Clinical trial NCT02001909: Effect of Neomycin on the Pharmacokinetics of Regorafenib
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Regorafenib
Neomycin
Cancer
Pharmacokinetics
Safety
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-12-05
Enrollment: 27
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

Brief summary: To investigate the effect of neomycin on the pharmacokinetics (PK) of regorafenib in healthy male subjects


Eligibility 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

Primary outcomes:
measure: AUC (area under the plasma concentration vs. time curve) for regorafenib
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose
measure: Cmax (maximum drug concentration) for regorafenib
timeFrame: 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 outcomes:
measure: AUC(0-24) (area under the plasma concentration vs. time curve) for regorafenib
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose
measure: AUC(0-tlast) (area under the plasma concentration vs. time curve) for regorafenib
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose
measure: AUC (area under the plasma concentration vs. time curve) for BAY75-7495 (M-2) and BAY81-8752 (M-5)
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose
measure: Cmax (maximum drug concentration) for M-2 and M-5
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose
measure: tmax (time to reach maximum drug concentration in plasma after single dose) for regorafenib, M-2 and M-5
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose
measure: tlast (time of last concentration above lower limit of quantification) for regorafenib, M-2 and M-5
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose
measure: t1/2 (half-life associated with the terminal slope) for regorafenib, M-2 and M-5
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168 and 192 hours post-dose
measure: 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)
timeFrame: 0-72 hours post dose
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Up to 30 days after last dose
Other outcomes:
Locations:
city: Berlin
country: Germany
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: