Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This trial will investigate the pharmacokinetics and safety of BI 695502 and to establish pharmacokinetic biosimilarity of BI 695502 compared to bevacizumab.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 695502 | Experimental | Subject to receive one intravenous (i.v.) infusion of BI 695502 |
|
| bevacizumab A | Active Comparator | Subject to receive one i.v. infusion of bevacizumab |
|
| bevacizumab B | Active Comparator | Subject to receive one i.v. infusion of bevacizumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 695502 | Drug | BI 695502 single i.v. infusion |
| |
| bevacizumab |
| 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 |
| 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. |
Not provided
Inclusion criteria:
Exclusion criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1302.1.002 Boehringer Ingelheim Investigational Site | Auckland NZ | New Zealand | ||||
| 1302.1.001 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28651442 | Derived | 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. |
Not provided
Not provided
Subjects were randomized in a 1:1:1 ratio to receive BI 695502, United States (US)-licensed Avastin® or European Union (EU)-approved Avastin®.
This was a randomized, single-blind, single-dose, parallel-arm, active comparator, Phase I clinical trial. The trial was planned to be conducted in two stages and subjects were to be randomly allocated in each stage. Based on the interim analysis finalized on 18 February 2013, the trial was closed after Stage 1, and Stage 2 was not conducted.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | BI 695502 (T) | Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion. |
| FG001 | United States (US)-Licensed Avastin® (R1) | Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion. |
| FG002 | European Union (EU)-Approved Avastin® (R2) | Subjects were administered a single dose of 25 microgram per millilitre (mg/mL) EU-approved Avastin® concentrate for solution for infusion. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated Set: All subjects who received at least one administration of trial medication were included in the safety evaluation.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | BI 695502 (T) | Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion. |
| BG001 | United States (US)-Licensed Avastin® (R1) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 (PK) set: The PK set included all subjects in the treated set (subjects who received at least one administration of trial medication) who provided at least one evaluable observation of a PK endpoint and had no important protocol violations relevant to the evaluation of PK biosimilarity. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram*hour/milliliter | Pharmacokinetic samples were collected predose, just before the end of the infusion, 2, 4, and 8 hours after the start of the infusion |
|
From first drug administration to end of trial; up to 99 days.
Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BI 695502 (T) | Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 11, 2013 | Oct 10, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 13, 2012 | Oct 10, 2019 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
bevacizumab single i.v. infusion |
|
| bevacizumab | Drug | bevacizumab single i.v. infusion |
|
| 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. |
| Christchurch |
| New Zealand |
Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion.
| BG002 | European Union (EU)-Approved Avastin® (R2) | Subjects were administered a single dose of 25 microgram per millilitre (mg/mL) EU-approved Avastin® concentrate for solution for infusion. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion. |
| OG001 | United States (US)-Licensed Avastin® (R1) | Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion. |
| OG002 | European Union (EU)-Approved Avastin® (R2) | Subjects were administered a single dose of 25 microgram per millilitre (mg/mL) EU-approved Avastin® concentrate for solution for infusion. |
|
|
|
| Secondary | 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 (PK) set: The PK set included all subjects in the treated set (subjects who received at least one administration of trial medication) who provided at least one evaluable observation of a PK endpoint and had no important protocol violations relevant to the evaluation of PK biosimilarity. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram*hour/milliliter | Pharmacokinetic samples were collected predose, just before the end of the infusion, 2, 4, and 8 hours after the start of the infusion |
|
|
|
|
| Secondary | 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 (PK) set: The PK set included all subjects in the treated set (subjects who received at least one administration of trial medication) who provided at least one evaluable observation of a PK endpoint and had no important protocol violations relevant to the evaluation of PK biosimilarity. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram/milliliter | Pharmacokinetic samples were collected predose, just before the end of the infusion, 2, 4, and 8 hours after the start of the infusion. |
|
|
|
|
| 0 |
| 30 |
| 0 |
| 30 |
| 25 |
| 30 |
| EG001 | United States (US)-Licensed Avastin® (R1) | Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion. | 0 | 30 | 0 | 30 | 19 | 30 |
| EG002 | European Union (EU)-Approved Avastin® (R2) | Subjects were administered a single dose of 25 microgram per millilitre(mg/mL) EU-approved Avastin® concentrate for solution for infusion. | 0 | 31 | 0 | 31 | 21 | 31 |
| Respiratory tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| ANOVA | Analysis of variance (ANOVA) model on the logarithmic scale including effects'treatment' and 'weight'. | gMean ratio | 91.67 | 2-Sided | 90 | 84.02 | 100.01 | (T/R2) * 100 | Equivalence | Commonly applied acceptance range for bioequivalence/biosimilarity is 80% to 125%. | Least squares estimates of log-transformed PK endpoint for T and R1 were back transformed to original scale to get adjusted point estimator and interval estimates for the ratio of the geometric means for treatments. |
| ANOVA | Analysis of variance (ANOVA) model on the logarithmic scale including effects'treatment' and 'weight'. | gMean ratio | 92.63 | 2-Sided | 90 | 85.18 | 100.74 | (R1/R2) * 100 | Equivalence | Commonly applied acceptance range for bioequivalence/biosimilarity is 80% to 125%. | Least squares estimates of log-transformed PK endpoint for T and R1 were back transformed to original scale to get adjusted point estimator and interval estimates for the ratio of the geometric means for treatments. |
| ANOVA | Analysis of variance (ANOVA) model on the logarithmic scale including effects'treatment' and 'weight'. | gMean ratio | 93.25 | 2-Sided | 90 | 87.12 | 99.81 | (T/R2) * 100 | Equivalence | Commonly applied acceptance range for bioequivalence/biosimilarity is 80% to 125%. | Least squares estimates of log-transformed PK endpoint for T and R1 were back transformed to original scale to get adjusted point estimator and interval estimates for the ratio of the geometric means for treatments. |
| ANOVA | Analysis of variance (ANOVA) model on the logarithmic scale including effects'treatment' and 'weight'. | gMean ratio | 91.85 | 2-Sided | 90 | 83.91 | 100.54 | (R1/R2) * 100 | Equivalence | Commonly applied acceptance range for bioequivalence/biosimilarity is 80% to 125%. | Least square estimates of log-transformed PK endpoint for R1 and R2 were back transformed to original scale to get adjusted point estimator and interval estimates for the inter-subject ratio of the geometric means for treatments. |