Drug InteractionsPhase 1NCT01925638
Effect of Ketoconazole on the Pharmacokinetics of Refametinib
A Phase 1 study testing BAY86-9766 and Ketoconazole in people with Drug Interactions, run by Bayer at 1 site in United States.
Trial summary
The purpose of this study is to see if there is a difference between the way your body absorbs and distributes BAY86-9766 when given alone or in combination with ketoconazole, a drug which may affect how much BAY86-9766 is absorbed, distributed or eliminated from the body Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Drug Interactions
- What is being tested?
- BAY86-9766 and Ketoconazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to Dec 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 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male subject
- Age: 18 to 45 years (inclusive) at the first screening examination / visit
- Body mass index (BMI): 18.5 to 32 kg/m² (inclusive)
- Ability to understand and follow study-related instructions. Subject, who is a sexually active man and has not been surgically sterilized, must consent that he uses a condom during intercourse and ensures that his female partner practices adequate contraception, or he must be willing to refrain from sexual intercourse from the beginning of the trial (signing of the informed consent) until 30 days after last study drug administration
Who cannot join
- Clinically significant disease or condition
- Retinal pathology or vien occlusion
- Left Ventricular ejection Fraction(LVEF) <60% (as measured at screening) by Multiple Gated Acquisition Scan(MUGA) or echocardiogram
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label Study in Healthy Male Subjects to Assess the Effect of a Strong CYP3A4 Inhibitor, Ketoconazole, on the Pharmacokinetics of Refametinib
The purpose of this study is to see if there is a difference between the way your body absorbs and distributes BAY86-9766 when given alone or in combination with ketoconazole, a drug which may affect how much BAY86-9766 is absorbed, distributed or eliminated from the body
- Conditions
- Drug Interactions
- Being tested
- BAY86-9766, Ketoconazole
- Keywords
- Healthy Volunteers, Refametinib, Ketoconazole, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY86-9766Drug
KetoconazoleDrug
| Study group | Role | What they receive |
|---|---|---|
| BAY86-9766 | Experimental | The study will be conducted in two parts and study treatments will be administered as follows: •Part A: Three subjects will be enrolled and will receive 10 mg of refametinib on Day 1. Once daily dosing of ketoconazole 400 mg will be initiated on Day 5 and will continue until Day 12 with 10 mg of refametinib administered concomitantly on Day 8 •Part B: Fifteen subjects will be enrolled and will receive refametinib doses of 10 mg, 20 mg or 30 mg on Days 1 and 8 with the same dose administered on both days. Refametinib dose for Part B will be based on safety and refametinib pharmacokinetics in Part A. Ketoconazole 400 mg will be administered once daily on Days 5 to 12. Subjects will stay in the investigational site for a total period of 15 consecutive days Receives: Drug: BAY86-9766; Drug: Ketoconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax(maximum observed drug concentration in measured matrix after single dose administration) of BAY86-9766
Measured: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
AUC(area under the concentration vs. time curve from zero to infinity after single (first) dose) of BAY86-9766
Measured: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
t1/2(half-life associated with the terminal slope) of BAY86-9766
Measured: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
Secondary outcomes (8)
Number of participants with adverse events as a measure of safety and tolerability
Measured: 2.5 months
AUC(0-tlast)(AUC from time 0 to the last data point > LLOQ) of BAY86-9766 and Metabolites M-11 and M-17
Measured: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
tmax(time to reach Cmax) of BAY86-9766 and Metabolites M-11 and M-17
Measured: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
tlast(time of last observed concentration value above lower limit of quantitation) of BAY86-9766 and Metabolites M-11 and M-17
Measured: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
Cmax(maximum observed drug concentration in measured matrix after single dose administration) of Metabolites M-11 and M-17
Measured: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
AUC(area under the concentration vs. time curve from zero to infinity after single (first) dose) of Metabolites M-11 and M-17
Measured: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
t1/2(half-life associated with the terminal slope) of Metabolites M-11 and M-17
Measured: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
CL/F(total body clearance of drug calculated after extravascular administration) of BAY 86-9766)
Measured: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2013 (estimated)
- Study startSep 2013
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug InteractionsStudies of the same condition, open and under way.
- More trials run by BayerThe 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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01925638
- Sponsor's protocol ID
- 14751
- Status last verified
- Jan 2014
- First submitted
- 16 Aug 2013
- Last updated
- 8 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study in Healthy Male Subjects to Assess the Effect of a Strong CYP3A4 Inhibitor, Ketoconazole, on the Pharmacokinetics of Refametinib
- ClinicalTrials.gov ID
- NCT01925638
- Acronym / sponsor ID
- 14751
- Conditions
- Drug Interactions
- Keywords
- Healthy Volunteers, Refametinib, Ketoconazole, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- Sep 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 20 Aug 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 see if there is a difference between the way your body absorbs and distributes BAY86-9766 when given alone or in combination with ketoconazole, a drug which may affect how much BAY86-9766 is absorbed, distributed or eliminated from the body
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BAY86-9766 | Experimental | Drug: BAY86-9766, Drug: KetoconazoleThe study will be conducted in two parts and study treatments will be administered as follows: •Part A: Three subjects will be enrolled and will receive 10 mg of refametinib on Day 1. Once daily dosing of ketoconazole 400 mg will be initiated on Day 5 and will continue until Day 12 with 10 mg of refametinib administered concomitantly on Day 8 •Part B: Fifteen subjects will be enrolled and will receive refametinib doses of 10 mg, 20 mg or 30 mg on Days 1 and 8 with the same dose administered on both days. Refametinib dose for Part B will be based on safety and refametinib pharmacokinetics in Part A. Ketoconazole 400 mg will be administered once daily on Days 5 to 12. Subjects will stay in the investigational site for a total period of 15 consecutive days |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy male subject
- Age: 18 to 45 years (inclusive) at the first screening examination / visit
- Body mass index (BMI): 18.5 to 32 kg/m² (inclusive)
- Ability to understand and follow study-related instructions. Subject, who is a sexually active man and has not been surgically sterilized, must consent that he uses a condom during intercourse and ensures that his female partner practices adequate contraception, or he must be willing to refrain from sexual intercourse from the beginning of the trial (signing of the informed consent) until 30 days after last study drug administration
Key exclusion criteria (3 listed)
- Clinically significant disease or condition
- Retinal pathology or vien occlusion
- Left Ventricular ejection Fraction(LVEF) <60% (as measured at screening) by Multiple Gated Acquisition Scan(MUGA) or echocardiogram
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 |
|---|---|---|
| BAY86-9766 | Drug | BAY86-9766 |
| Ketoconazole | Drug | BAY86-9766 |
Primary outcome
Cmax(maximum observed drug concentration in measured matrix after single dose administration) of BAY86-9766
Time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
AUC(area under the concentration vs. time curve from zero to infinity after single (first) dose) of BAY86-9766
Time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
t1/2(half-life associated with the terminal slope) of BAY86-9766
Time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
8 secondary outcomes
Number of participants with adverse events as a measure of safety and tolerability
Time frame: 2.5 months
AUC(0-tlast)(AUC from time 0 to the last data point > LLOQ) of BAY86-9766 and Metabolites M-11 and M-17
Time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
tmax(time to reach Cmax) of BAY86-9766 and Metabolites M-11 and M-17
Time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
tlast(time of last observed concentration value above lower limit of quantitation) of BAY86-9766 and Metabolites M-11 and M-17
Time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
Cmax(maximum observed drug concentration in measured matrix after single dose administration) of Metabolites M-11 and M-17
Time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
AUC(area under the concentration vs. time curve from zero to infinity after single (first) dose) of Metabolites M-11 and M-17
Time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
t1/2(half-life associated with the terminal slope) of Metabolites M-11 and M-17
Time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
CL/F(total body clearance of drug calculated after extravascular administration) of BAY 86-9766)
Time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
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 8 Jan 2014.
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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.
Bayer Study Director study director
Bayer
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 BAY86-9766 and Ketoconazole in people with Drug Interactions, run by Bayer 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 4 inclusion and 3 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 8 Jan 2014. 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?
Cmax(maximum observed drug concentration in measured matrix after single dose administration) of BAY86-9766 (time frame: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose). The study lists 3 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 8 Jan 2014.