Clinical trial NCT02538393: Relative Bioavailability of Sorafenib Tablet for Oral Suspension
Official title: An Open Label, Randomized, Four-way Crossover Study in Healthy Male Subjects to Assess the Relative Bioavailability of Sorafenib Tablet for Oral Suspension Compared to Marketed Tablet and to Investigate the Pharmacokinetics of Sorafenib Tablet for Oral Suspension Including Food Effect and Dose Proportionality
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Biological Availability
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-09-02
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The primary objective of the study is to

• Investigate the relative bioavailability of sorafenib as 400 mg (4 x 100 mg) tablet for oral suspension formulation in comparison to 400 mg (2 x 200 mg) marketed tablet formulation.

The secondary objectives of this study are to

* Evaluate the dose proportionality in sorafenib pharmacokinetics for sorafenib tablet for oral suspension formulation after administration of 200 mg (2 x 100 mg) and 400 mg (4 x 100 mg) dose of sorafenib in fasted state
* Evaluate the effect of food on the pharmacokinetics of the tablet for oral suspension formulation after administration of a single dose of 400 mg sorafenib (4 x 100mg)
* Evaluate the taste and palatability of sorafenib (both formulations)
* Assess the safety and tolerability of sorafenib tablet for oral suspension 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 18.0 (inclusive) and 32.0 kg / m² (inclusive).
* Non-smoker or former smoker who has stopped smoking at least 3 months before the first study drug administration
* Ability to understand and follow study-related instructions
* Any subject who is a sexually active man and has not been surgically sterilized must consent to use a condom during intercourse and ensure that his female partner practices adequate contraception, or he must be willing to refrain from sexual intercourse from the beginning of the trial until 30 days after last study drug administration.

Exclusion Criteria:

* Medical and surgical history:

  * Failure of a major organ system or a medical disorder that would impair the subject's ability to complete the study or that would alter the absorption and pharmacokinetics of the study drug
  * Active infections or other medical, psychological or social problems of sufficient severity to limit full compliance with the trial
  * Known severe allergies, non-allergic drug reactions, or multiple drug allergies
  * History of clinically significant metabolic, renal, hepatic, or cardiovascular disease or central nervous system disorder
  * Clinically significant illness within 30 days before first study drug administration.
  * Febrile illness within 1 week before the first study drug administration
  * Known hypersensitivity to study drug
  * Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal
* Electrocardiogram (ECG), blood pressure, heart rate:

  * Clinically relevant findings in the ECG (e.g. a second- or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QTc-interval over 450 msec)
* Laboratory examination:

  * Clinically relevant deviations of the screened laboratory parameters from reference ranges (especially for gamma-GT, ALT, AST, or bilirubin)
  * Positive results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), human immune deficiency virus antibodies (anti-HIV)

Primary outcomes:
measure: Area Under the Concentration Versus Time Curve From Zero to Last Data Point Greater Than Lower Limit of Quantitation (LLOQ) of Sorafenib in Plasma (AUC[0-tlast]) After Single Oral Dose
timeFrame: Pre-dose (0 hour) to 120 hours post-dose
measure: Maximum Observed Drug Concentration After Single Dose Administration (Cmax) of Sorafenib in Plasma
timeFrame: Pre-dose (0 hour) to 120 hours post-dose
Secondary outcomes:
measure: Maximum Observed Drug Concentration After Single Dose Administration Divided by Dose (Cmax/D) of Sorafenib in Plasma
timeFrame: Pre-dose (0 hour) to 120 hours post-dose
measure: Area Under the Concentration Versus Time Curve From Zero to Infinity After Single Dose (AUC) of Sorafenib in Plasma
timeFrame: Pre-dose (0 hour) to 120 hours post-dose
measure: Area Under the Concentration Versus Time Curve From Zero to Infinity After Single Dose Divided by Dose (AUC/D) of Sorafenib in Plasma
timeFrame: Pre-dose (0 hour) to 120 hours post-dose
measure: Area Under the Concentration Versus Time Curve From Zero to Last Data Point Divided by Dose (AUC[0-tlast]/D) of Sorafenib in Plasma
timeFrame: Pre-dose (0 hour) to 120 hours post-dose
measure: Total Body Clearance of Sorafenib Calculated After Extravascular Administration (CL/F)
timeFrame: Pre-dose (0 hour) to 120 hours post-dose
measure: Time to Reach Maximum Concentration (tmax) of Sorafenib in Plasma
timeFrame: Pre-dose (0 hour) to 120 hours post-dose
measure: Half-life Associated With the Terminal Slope (t1/2) of Sorafenib in Plasma
timeFrame: Pre-dose (0 hour) to 120 hours post-dose
measure: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From start of study treatment up to 30 days after the last sorafenib dose administration
measure: Number of Subjects With Various Acceptance Regarding the Taste and Palatability of the Tablet Formulations
timeFrame: Within 5 to 10 min of each administration of sorafenib
Other outcomes:
Locations:
city: Berlin
country: Germany
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: