Clinical trial NCT02332031: Sorafenib Drug Drug Interaction Study in Healthy Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interactions
Keywords: Sorafenib, levothyroxine, drug interaction, pharmacokinetics, healthy volunteer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-01-06
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

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


Eligibility criteria: 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

Primary outcomes:
measure: Area under the concentration vs. time curve from zero to infinity after single (first) dose (AUC) of sorafenib
timeFrame: 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 outcomes:
measure: AUC from time 0 to the last data point > LLOQ (AUC(0-tlast))of Sorafenib and metabolite M-2
timeFrame: 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
measure: Maximum observed drug concentration in measured matrix after single dose administration (Cmax) of Sorafenib and metabolite M-2
timeFrame: 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
measure: Time to reach Cmax (in case of two identical Cmax values, the first tmax will be used) (Tmax Sorafenib) and metabolite M-2
timeFrame: 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
measure: Half-life associated with the terminal slope (t1/2) of Sorafenib and metabolite M-2
timeFrame: 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
measure: Apparent volume of distribution at steady state after extravascular administration (Vss/F) of Sorafenib
timeFrame: 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
measure: Total body clearance of Sorafenib calculated after extravascular administration (CL/F)
timeFrame: 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
measure: AUC of metabolite M-2
timeFrame: 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
measure: Metabolite to parent AUC(0-tlast) ratios
timeFrame: 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
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Up to 15 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: