Sorafenib Drug Drug Interaction Study in Healthy Male Subjects

An Open-label Study in Healthy Male Subjects to Assess the Effect of Hyperthyroidism Mimicked by Oral Dosing of Levothyroxine on the Pharmacokinetics of Sorafenib

To evaluate the effect of levothyroxine on the absorption, distribution, metabolization and elimination of sorafenib and safety in healthy male subjects

Study Overview

• Status: Completed
• Conditions: Drug Interactions
• Intervention / Treatment: Drug: Sorafenib (Nexavar, BAY43-9006); Drug: Levothyroxine

• Study Type: Interventional
• Enrollment (Actual): 25
• 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 Criteria:

• Healthy male subjects between the ages of 18 (inclusive) and 45 years (inclusive) at the first screening visit.
• Body mass index (BMI) between 18.5 (inclusive) to 30.0 kg / m² (inclusive) with body weight ≥ 65kg.
• Normal thyroid function indicated by thyroid examination to include total and free T3 (Triiodothyronine) , T4 (total and free Thyroxine, levothyroxine), TSH (Thyroid stimulating hormone), anti-TSH-receptor (anti-TSHR) antibody, anti-thyroperoxidase (anti-TPO) antibody, anti-thyroglobulin antibody (anti-ATA) as well as thyroid ultrasound.

Exclusion Criteria:

• History of clinically significant metabolic, renal, hepatic, or central nervous system disorder such as seizure, psychosis and sleep disorders.
• History of cardiovascular diseases including arrhythmia, hypertension, ischemia, etc.
• Known or suspected cardiovascular disease including potential risk of atrioventricular (AV) block, arrhythmia, etc. with or without a formal cardiologist consultation.
• Subjects who had received iodine containing contrast medium within 2 months before first study drug administration.
• Use of systemic or topical medicines or substances which might affect the study drug(s) must be avoided

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib (Nexavar, BAY43-9006) & Levothyroxine; Sorafenib be administrated without and with levothyroxine orally	Drug: Sorafenib (Nexavar, BAY43-9006); Single dose of 400 mg orally on Period 1 Day 1 and Period 2 Day 11; Drug: Levothyroxine; Single dose of 300 mcq orally from Period 2 Day 1 to Period 2 Day 14

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration vs. time curve from zero to infinity after single (first) dose (AUC) of sorafenib	Period 1 Day 1 and Period 2 Day 11: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 h post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC from time 0 to the last data point > LLOQ (AUC(0-tlast))of Sorafenib and metabolite M-2	Period 1 Day 1 and Period 2 Day 11: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 h post-dose
Maximum observed drug concentration in measured matrix after single dose administration (Cmax) of Sorafenib and metabolite M-2	Period 1 Day 1 and Period 2 Day 11: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 h post-dose
Time to reach Cmax (in case of two identical Cmax values, the first tmax will be used) (Tmax Sorafenib) and metabolite M-2	Period 1 Day 1 and Period 2 Day 11: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 h post-dose
Half-life associated with the terminal slope (t1/2) of Sorafenib and metabolite M-2	Period 1 Day 1 and Period 2 Day 11: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 h post-dose
Apparent volume of distribution at steady state after extravascular administration (Vss/F) of Sorafenib	Period 1 Day 1 and Period 2 Day 11: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 h post-dose
Total body clearance of Sorafenib calculated after extravascular administration (CL/F)	Period 1 Day 1 and Period 2 Day 11: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 h post-dose
AUC of metabolite M-2	Period 1 Day 1 and Period 2 Day 11: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 h post-dose
Metabolite to parent AUC(0-tlast) ratios	Period 1 Day 1 and Period 2 Day 11: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 h post-dose
Number of participants with adverse events as a measure of safety and tolerability	Up to 15 weeks

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: January 5, 2015
• First Submitted That Met QC Criteria: January 5, 2015
• First Posted (Estimate): January 6, 2015

Study Record Updates

• Last Update Posted (Estimate): October 12, 2015
• Last Update Submitted That Met QC Criteria: October 9, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Sorafenib, levothyroxine, drug interaction, pharmacokinetics, healthy volunteer
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 17436; 2014-001907-36 (EudraCT Number)