Safety and Tolerability Study of BIBF 1120 as Intravenous Infusion and Absolute Bioavailability of BIBF 1120 as Soft Gelatine Capsule in Healthy Subjects

Study Overview
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Brief Summary
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The primary objective of this trial was to assess the safety and tolerability of BIBF 1120 administered as intravenous (iv) infusions of 1, 3, 10, and 20 mg, and to assess the absolute bioavailability of orally administered 100 mg BIBF 1120 as soft gelatine capsules. A secondary objective was the exploration of the pharmacokinetic (PK) of BIBF 1120 after single iv dosing, including dose proportionality.

Official Title
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Safety and Tolerability of Single Rising Doses of 1 mg, 3 mg, 10 mg and 20 mg of BIBF 1120 as Intravenous Infusion (Single-blind, Placebocontrolled at Each Dose Group) and Absolute Bioavailability of 100 mg BIBF 1120 as Soft Gelatine Capsule (Intra-individual Comparison)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBF 1120 soft gelatine capsule
* Drug: BIBF 1120 intravenous solution
* Drug: Placebo ampoule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate), 12-lead ECG, and clinical laboratory tests Age ≥18 years and ≤50 years Body mass index (BMI) ≥18.5 and ≤29.9 kg/m2 Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation Exclusion Criteria: Any finding from medical examination (including blood pressure, pulse rate, ECG) deviating from normal and of clinical relevance History of or current gastrointestinal, hepatic (including Gilbert's syndrome and history of bilirubin increases) renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders History of relevant orthostatic hypotension, fainting spells, and blackouts Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy or its excipients) which is deemed relevant to the trial as judged by the investigator History of any bleeding disorder including prolonged or habitual bleeding, other haematologic disease or cerebral bleeding (e.g. after a car accident) or commotio cerebri Intake of drugs with a long half-life (>24 h) within 1 month prior to administration or during the trial Use of any drugs which might influence the results of the trial within 14 days prior to administration or during the trial Participation in another trial with an investigational drug within 2 months prior to administration or during the trial Smoker (>10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days Alcohol abuse (>30 g/day) Drug abuse Blood donation (>150 mL within 4 weeks prior to administration or during the trial) Excessive physical activities within 5 days prior to administration or during the trial Any laboratory value outside the reference range that is of clinical relevance Male subjects refusing to minimise the risk of female partners becoming pregnant from the first dosing day until 3 months after completion of the study. Acceptable methods of contraception for male volunteers include vasectomy no less than 3 months prior to administration, barrier contraception, or a medically accepted contraceptive method. Acceptable methods of contraception for female partners of male volunteers include intra-uterine device, tubal ligation, hormonal contraceptive for at least 2 months and diaphragm with spermicide. Homozygous genotype status for UGT1A1*28, *60 (Gilbert polymorphisms)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo ampoule<br> <br> |
| Active Comparator: BIBF 1120 intravenous<br> | Drug: BIBF 1120 intravenous solution<br> <br> |
| Experimental: BIBF 1120 capsule<br> | Drug: BIBF 1120 soft gelatine capsule<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) |  | Up to 48 hours after drug administration | 
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) |  | Up to 48 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured concentration of the analyte in plasma (Cmax) |  | Up to 48 hours after drug administration | 
| Time from dosing to the maximum concentration of the analyte in plasma (tmax) |  | Up to 48 hours after drug administration | 
| %AUCtz-∞ (calculated from AUC0-∞ and AUC0-tz ) |  | Up to 48 hours after drug administration | 
| Terminal rate constant in plasma (λz) |  | Up to 48 hours after drug administration | 
| Terminal half-life of the analyte in plasma (t1/2) |  | Up to 48 hours after drug administration | 
| Mean residence time of the analyte in the body after oral administration (MRTpo) |  | Up to 48 hours after drug administration | 
| Mean residence time of the analyte in the body after iv administration (MRT) |  | Up to 48 hours after drug administration | 
| Apparent clearance of the analyte in plasma after extravascular administration (CL/F) |  | Up to 48 hours after drug administration | 
| Apparent clearance of the analyte in plasma after intravenous administration (CL) |  | Up to 48 hours after drug administration | 
| Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) |  | Up to 48 hours after drug administration | 
| Apparent volume of distribution during the terminal phase λz following an intravenous dose (Vz) |  | Up to 48 hours after drug administration | 
| Apparent volume of distribution at steady-state following an intravenous dose (Vss) |  | Up to 48 hours after drug administration | 
| Amount of analyte that is eliminated in urine within the time interval t1 to t2 (Aet1-t2) |  | Up to 48 hours after drug administration | 
| Fraction of analyte excreted in urine within the time interval t1 to t2, in percentage of dose (fet1-t2) |  | Up to 48 hours after drug administration | 
| Renal clearance of analyte within the time interval t1 to t2 (CLR,t1-t2) |  | Up to 48 hours after drug administration | 
| Change from baseline in physical examination |  | Baseline, day 46 | 
| Change from baseline in vital signs (BP, PR) |  | Baseline, day 46 | 
| Change from baseline in 12-lead ECG (electrocardiogram) |  | Baseline, day 46 | 
| Change from baseline in clinical laboratory test (hematology, clinical chemistry and urinalysis) |  | Baseline, day 46 | 
| Number of Participants with Serious and Non-Serious Adverse Events |  | Up to day 46 | 
| Assessment of tolerability by investigator on a four point scale (good, satisfactory, not satisfactory, bad) |  | Up to day Day 46 |