Pharmacokinetics and Safety Study of BI 695502 in Healthy Subjects

Pharmacokinetics and Safety of BI 695502 in Healthy Subjects: a Randomized, Single-blind, Single-dose, Parallel-arm, Active-comparator Clinical Phase I Study

This trial will investigate the pharmacokinetics and safety of BI 695502 and to establish pharmacokinetic biosimilarity of BI 695502 compared to bevacizumab.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BI 695502; Drug: bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland NZ, New Zealand
    • 1302.1.002 Boehringer Ingelheim Investigational Site
  • Christchurch, New Zealand
    • 1302.1.001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion criteria:

1. Healthy males.
2. Complete medical history, including physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests.
3. Aged 21 to 50 years.
4. Body mass index below or equal to 30.
5. Body weight 65 to 95 kg, inclusive.

Exclusion criteria:

1. Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance.
2. Any evidence of a clinically relevant concomitant disease, as judged by the investigator.
3. History of relevant orthostatic hypotension, fainting spells, or blackouts.
4. Chronic or relevant acute infections.
5. History of relevant allergy/hypersensitivity (including allergy to the study medications or its excipients).
6. Intake of prescribed or over-the-counter drugs within less than 6 half-lives of the respective drug prior to study drug administration or during the trial.
7. Participation in another trial with a study medication within two months prior to administration or during the trial (six half-lives).
8. Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day).
9. Inability to refrain from smoking during days of confinement at the study center.
10. Current alcohol abuse as judged by the investigator.
11. Current drug abuse, as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BI 695502; Subject to receive one intravenous (i.v.) infusion of BI 695502	Drug: BI 695502; BI 695502 single i.v. infusion
ACTIVE_COMPARATOR: bevacizumab A; Subject to receive one i.v. infusion of bevacizumab	Drug: bevacizumab; bevacizumab single i.v. infusion
ACTIVE_COMPARATOR: bevacizumab B; Subject to receive one i.v. infusion of bevacizumab	Drug: bevacizumab; bevacizumab single i.v. infusion

What is the study measuring?

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-∞).	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented as adjusted geometric mean (gMean) and geometric coefficient of variation (%) (gCV%). Adjustment were made for treatment effect and weight.	Pharmacokinetic samples were collected predose, just before the end of the infusion, 2, 4, and 8 hours after the start of the infusion

Secondary 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 to the Time of the Last Quantifiable Data Point (AUC0-tz)	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 is presented as adjusted geometric mean (gMean) and geometric coefficient of variation (%) (gCV%). Adjustment was made for treatment effect and weight.	Pharmacokinetic samples were collected predose, just before the end of the infusion, 2, 4, and 8 hours after the start of the infusion
Maximum Measured Concentration of the Analyte in Plasma (Cmax)	Maximum measured concentration of the analyte in plasma (Cmax) is presented as adjusted geometric mean (gMean) and geometric coefficient of variation (%) (gCV%). Adjustment was made for treatment effect and weight.	Pharmacokinetic samples were collected predose, just before the end of the infusion, 2, 4, and 8 hours after the start of the infusion.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Hettema W, Wynne C, Lang B, Altendorfer M, Czeloth N, Lohmann R, Athalye S, Schliephake D. A randomized, single-blind, Phase I trial (INVICTAN-1) assessing the bioequivalence and safety of BI 695502, a bevacizumab biosimilar candidate, in healthy subjects. Expert Opin Investig Drugs. 2017 Aug;26(8):889-896. doi: 10.1080/13543784.2017.1347635. Epub 2017 Jul 12.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2012
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): November 1, 2012

Study Registration Dates

• First Submitted: May 22, 2012
• First Submitted That Met QC Criteria: May 25, 2012
• First Posted (ESTIMATE): May 30, 2012

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2019
• Last Update Submitted That Met QC Criteria: October 21, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 1302.1