Drug Interactions
Conditions
Keywords
Sorafenib, levothyroxine, drug interaction, pharmacokinetics, healthy volunteer
Brief summary
To evaluate the effect of levothyroxine on the absorption, distribution, metabolization and elimination of sorafenib and safety in healthy male subjects
Interventions
DRUGSorafenib (Nexavar, BAY43-9006)
Single dose of 400 mg orally on Period 1 Day 1 and Period 2 Day 11
DRUGLevothyroxine
Single dose of 300 mcq orally from Period 2 Day 1 to Period 2 Day 14
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| Number of participants with adverse events as a measure of safety and tolerability | Up to 15 weeks |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Germany
Outcome results
None listed