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Effect of Ketoconazole on the Pharmacokinetics of Refametinib

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01925638
First received: August 16, 2013
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Drug Interactions
Drug: BAY86-9766
Drug: Ketoconazole
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 2.5 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: September 2013
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01925638

Locations
United States, Texas
Austin, Texas, United States, 78744
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01925638     History of Changes
Other Study ID Numbers: 14751
Study First Received: August 16, 2013
Last Updated: January 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Healthy Volunteers
Refametinib
Ketoconazole
Pharmacokinetics

Additional relevant MeSH terms:
Ketoconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014