Effect of Neomycin on the Pharmacokinetics of Regorafenib

Study Overview
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Brief Summary
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To investigate the effect of neomycin on the pharmacokinetics (PK) of regorafenib in healthy male subjects

Official Title
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Single-center, Open-label, Non-randomized, Two-period Sequential Treatment Study to Assess the Effect of Neomycin on the Pharmacokinetics of Regorafenib in Healthy Male Subjects

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: Regorafenib (Stivarga, BAY73-4506)
* Drug: Neomycin


Participation Criteria
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Eligibility Criteria
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Inclusion: Healthy male subjects Age: 18 to 45 years (inclusive) at the first screening examination/visit Body mass index (BMI): above/equal 18 and below 30 kg / m² Confirmation of the subject's health insurance coverage prior to the first screening examination/visit Subjects enrolled in this study must use adequate barrier birth control measures prior to, during the course of the study, and 3 months after the last administration of regorafenib. An adequate contraception includes the use of condoms or a vasectomy. In addition, adequate birth control measures for the subject's partner is required, such as a hormonal contraception with implants or combined oral contraceptives, certain intrauterine devices, bilateral tubal ligation, or hysterectomy. Exclusion: Known or suspected hypersensitivity to regorafenib and/or neomycin Any illness or medical condition that is unstable or could jeopardize the safety of the subject and his compliance in the study Clinically significant illness within 30 days prior to Day 1, Period 1. Regular use of medicines at the time of screening, including herbal supplements and high dose vitamins Smoking; however, former smokers who have stopped smoking at least 3 months before the first study drug administration may be included Clinically relevant findings in the electrocardiogram (ECG) Clinically relevant findings in the complete physical examination Positive results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), human immune deficiency virus antibodies (anti-HIV 1+2) at screening. Positive urine drug screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regorafenib<br> | Drug: Regorafenib (Stivarga, BAY73-4506)<br>* single oral dose (s.d.) 160 mg (four 40 mg tablets) of regorafenib on two occasions (Day 1, Period 1, and Day 1, Period 2) separated by a washout period of at least 14 days<br>|
| Experimental: Neomycin<br> | Drug: Neomycin<br>* 1 g tid (three times a day) regimen of Neomycin (oral) on five days in Period 2 starting 4 days before regorafenib intake on day 1 in period 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (area under the plasma concentration vs. time curve) for regorafenib |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose | 
| Cmax (maximum drug concentration) for regorafenib |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-24) (area under the plasma concentration vs. time curve) for regorafenib |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 
| AUC(0-tlast) (area under the plasma concentration vs. time curve) for regorafenib |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose | 
| AUC (area under the plasma concentration vs. time curve) for BAY75-7495 (M-2) and BAY81-8752 (M-5) |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose | 
| Cmax (maximum drug concentration) for M-2 and M-5 |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose | 
| tmax (time to reach maximum drug concentration in plasma after single dose) for regorafenib, M-2 and M-5 |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose | 
| tlast (time of last concentration above lower limit of quantification) for regorafenib, M-2 and M-5 |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose | 
| t1/2 (half-life associated with the terminal slope) for regorafenib, M-2 and M-5 |  | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose | 
| AE,ur(0-72) (amount of drug excreted via urine during the collection interval 0-72 hours post administration) for metabolites BAY86-6651 (M-7) and BAY86-6652 (M-8) |  | 0-72 hours post dose | 
| Number of participants with adverse events as a measure of safety and tolerability |  | Up to 30 days after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Regorafenib, Neomycin, Cancer, Pharmacokinetics, Safety