Effect of Neomycin on the Pharmacokinetics of Regorafenib

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

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

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Regorafenib (Stivarga, BAY73-4506); Drug: Neomycin

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regorafenib	Drug: Regorafenib (Stivarga, BAY73-4506); 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
Experimental: Neomycin	Drug: Neomycin; 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.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: November 28, 2013
• First Submitted That Met QC Criteria: November 28, 2013
• First Posted (Estimate): December 5, 2013

Study Record Updates

• Last Update Posted (Estimate): August 13, 2015
• Last Update Submitted That Met QC Criteria: August 12, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Safety; Cancer; Pharmacokinetics; Regorafenib; Neomycin
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Neomycin
• Other Study ID Numbers: 16675; 2013-001721-18 (EudraCT Number)