Effect of Ketoconazole on the Pharmacokinetics of Refametinib
Study Details
Study Description
Brief 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BAY86-9766 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 |
Drug: BAY86-9766
Drug: Ketoconazole
|
Outcome Measures
Primary Outcome Measures
- Cmax(maximum observed drug concentration in measured matrix after single dose administration) of BAY86-9766 [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 [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 [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 Outcome Measures
- Number of participants with adverse events as a measure of safety and tolerability [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 [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 [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 [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 [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 [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 [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) [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]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy male subject
-
Age: 18 to 45 years (inclusive) at the first screening examination / visit
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Body mass index (BMI): 18.5 to 32 kg/m² (inclusive)
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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
Exclusion Criteria:
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Austin | Texas | United States | 78744 |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 14751