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

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)

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo ampoule; Drug: BIBF 1120 intravenous solution; Drug: BIBF 1120 soft gelatine capsule

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Healthy males according to the following criteria:

1. Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate), 12-lead ECG, and clinical laboratory tests
2. Age ≥18 years and ≤50 years
3. Body mass index (BMI) ≥18.5 and ≤29.9 kg/m2
4. Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation

Exclusion Criteria:

1. Any finding from medical examination (including blood pressure, pulse rate, ECG) deviating from normal and of clinical relevance
2. History of or current gastrointestinal, hepatic (including Gilbert's syndrome and history of bilirubin increases) renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
3. History of relevant orthostatic hypotension, fainting spells, and blackouts
4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
5. Chronic or relevant acute infections
6. History of allergy/hypersensitivity (including drug allergy or its excipients) which is deemed relevant to the trial as judged by the investigator
7. 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
8. Intake of drugs with a long half-life (>24 h) within 1 month prior to administration or during the trial
9. Use of any drugs which might influence the results of the trial within 14 days prior to administration or during the trial
10. Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
11. Smoker (>10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days
12. Alcohol abuse (>30 g/day)
13. Drug abuse
14. Blood donation (>150 mL within 4 weeks prior to administration or during the trial)
15. Excessive physical activities within 5 days prior to administration or during the trial
16. Any laboratory value outside the reference range that is of clinical relevance
17. 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.
18. Homozygous genotype status for UGT1A1*28, *60 (Gilbert polymorphisms)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: July 2, 2014
• First Submitted That Met QC Criteria: July 2, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): July 18, 2014
• Last Update Submitted That Met QC Criteria: July 17, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Nintedanib
• Other Study ID Numbers: 1199.75