Relative Bioavailability of Sorafenib Tablet for Oral Suspension

NCT ID: NCT02538393

Last Updated: 2017-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-20
• Study Completion Date: 2016-06-15

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

Conditions

Biological Availability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Treatment A-C-B-D

Subjects received a single oral dose of 400 mg sorafenib marketed tablets (2 \* 200 mg) in fasting state (Treatment A) in the first intervention period; followed by a single oral dose of 200 mg sorafenib tablets for oral suspension (2 \* 100 mg) in fasting state (Treatment C) in the second intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) in fasting state (Treatment B) in the third intervention period; and then a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.

Group Type: EXPERIMENTAL

Sorafenib (BAY43-9006) Film-coated tablet

Intervention Type: DRUG

Subjects received a single oral dose of 400 mg sorafenib marketed tablets (2 \* 200 mg) in fasting state in Treatment A

Sorafenib (BAY43-9006) Oral suspension

Intervention Type: DRUG

Treatment C: Subjects received a single oral dose of 200 mg sorafenib tablets for oral suspension (2 \* 100 mg) in fasting state in the second intervention period; Treatment B: Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) in fasting state in the third intervention period; Treatment D: Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) after a high-fat, high-calorie breakfast (fed state) in the fourth intervention period.

Treatment B-A-D-C

Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) in fasting state (Treatment B) in the first intervention period; followed by a single oral dose of 400 mg sorafenib marketed tablets (2 \* 200 mg) in fasting state (Treatment A) in the second intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the third intervention period; and then a single oral dose of 200 mg sorafenib tablets for oral suspension (2 \* 100 mg) in fasting state (Treatment C) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.

Group Type: EXPERIMENTAL

Sorafenib (BAY43-9006) Film-coated tablet

Intervention Type: DRUG

Subjects received a single oral dose of 400 mg sorafenib marketed tablets (2 \* 200 mg) in fasting state in Treatment A

Sorafenib (BAY43-9006) Oral suspension

Intervention Type: DRUG

Treatment C: Subjects received a single oral dose of 200 mg sorafenib tablets for oral suspension (2 \* 100 mg) in fasting state in the second intervention period; Treatment B: Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) in fasting state in the third intervention period; Treatment D: Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) after a high-fat, high-calorie breakfast (fed state) in the fourth intervention period.

Treatment C-D-A-B

Subjects received a single oral dose of 200 mg sorafenib tablets for oral suspension (2 \* 100 mg) in fasting state (Treatment C) in the first intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the second intervention period; followed by a single oral dose of 400 mg sorafenib marketed tablets (2 \* 200 mg) in fasting state (Treatment A) in the third intervention period; and then a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) in fasting state (Treatment B) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.

Group Type: EXPERIMENTAL

Sorafenib (BAY43-9006) Film-coated tablet

Intervention Type: DRUG

Subjects received a single oral dose of 400 mg sorafenib marketed tablets (2 \* 200 mg) in fasting state in Treatment A

Sorafenib (BAY43-9006) Oral suspension

Intervention Type: DRUG

Treatment C: Subjects received a single oral dose of 200 mg sorafenib tablets for oral suspension (2 \* 100 mg) in fasting state in the second intervention period; Treatment B: Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) in fasting state in the third intervention period; Treatment D: Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) after a high-fat, high-calorie breakfast (fed state) in the fourth intervention period.

Treatment D-B-C-A

Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the first intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) in fasting state (Treatment B) in the second intervention period; followed by a single oral dose of 200 mg sorafenib tablets for oral suspension (2 \* 100 mg) in fasting state (Treatment C) in the third intervention period; and then a single oral dose of 400 mg sorafenib marketed tablets (2 \* 200 mg) in fasting state (Treatment A) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.

Group Type: EXPERIMENTAL

Sorafenib (BAY43-9006) Film-coated tablet

Intervention Type: DRUG

Subjects received a single oral dose of 400 mg sorafenib marketed tablets (2 \* 200 mg) in fasting state in Treatment A

Sorafenib (BAY43-9006) Oral suspension

Intervention Type: DRUG

Treatment C: Subjects received a single oral dose of 200 mg sorafenib tablets for oral suspension (2 \* 100 mg) in fasting state in the second intervention period; Treatment B: Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) in fasting state in the third intervention period; Treatment D: Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) after a high-fat, high-calorie breakfast (fed state) in the fourth intervention period.

Interventions

Sorafenib (BAY43-9006) Film-coated tablet

Subjects received a single oral dose of 400 mg sorafenib marketed tablets (2 \* 200 mg) in fasting state in Treatment A

Intervention Type: DRUG

Sorafenib (BAY43-9006) Oral suspension

Treatment C: Subjects received a single oral dose of 200 mg sorafenib tablets for oral suspension (2 \* 100 mg) in fasting state in the second intervention period; Treatment B: Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) in fasting state in the third intervention period; Treatment D: Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 \* 100 mg) after a high-fat, high-calorie breakfast (fed state) in the fourth intervention period.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Berlin, , Germany

Countries

Germany

Other Identifiers

2015-002083-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

18175

Identifier Type: -

Identifier Source: org_study_id