Sorafenib Drug Drug Interaction Study in Healthy Male Subjects
Phase 1
Completed
- Conditions
- Drug Interactions
- Interventions
- Registration Number
- NCT02332031
- Lead Sponsor
- Bayer
- Brief Summary
To evaluate the effect of levothyroxine on the absorption, distribution, metabolization and elimination of sorafenib and safety in healthy male subjects
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 25
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sorafenib (Nexavar, BAY43-9006) & Levothyroxine Sorafenib (Nexavar, BAY43-9006) Sorafenib be administrated without and with levothyroxine orally Sorafenib (Nexavar, BAY43-9006) & Levothyroxine Levothyroxine Sorafenib be administrated without and with levothyroxine orally
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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