Neoplasms
Conditions
Keywords
Regorafenib, Neomycin, Cancer, Pharmacokinetics, Safety
Brief summary
To investigate the effect of neomycin on the pharmacokinetics (PK) of regorafenib in healthy male subjects
Interventions
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
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.
Sponsors
Study design
Eligibility
Inclusion criteria
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Germany