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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-005049-29 | EudraCT Number |
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The primary objective of this trial is to investigate the safety and tolerability of BI 1467335 in healthy male and female subjects following oral administration of multiple rising doses over 28 days.
Secondary objectives are the exploration of the pharmacokinetics (PK) and target engagement biomarkers of BI 1467335 after multiple dosing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 1467335 10 mg (low dose) | Experimental |
| |
| BI 1467335 15 mg (medium dose) | Experimental |
| |
| BI 1467335 20 mg (high dose) | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 1467335 | Drug |
| ||
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Investigator Defined Drug-related Adverse Events | Number of subjects with investigator defined drug-related adverse events (AEs) is reported. | From first day of study drug administration until 20 days after last dose of study drug administration, up to 48 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Cmax is the maximum measured concentration of BI 1467335 in plasma after administration of the first dose. | 0:00 hour (h) (within 30 minutes prior to dosing) and 0:15 h, 0:30 h, 0:45 h, 1:00 h, 1:30 h, 2:00 h, 3:00 h, 4:00 h, 6:00 h, 8:00 h, 10:00 h, 12:00 h and 24:00 h after drug administration on Day 1. |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CRS Clinical Research Services Mannheim GmbH | Mannheim | 68167 | Germany |
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| Label | URL |
|---|---|
| Related Info | View source |
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All subjects were screened for eligibility to participate in trial. Subjects attended specialist sites to ensure that they (the subjects) met all implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial drug if any of the specific entry criteria was violated.
This was a double-blind, randomised, placebo-controlled within parallel dose groups, multiple dose trial.Only male subjects & postmenopausal or surgically sterilised female subjects were included into trial because at time of trial start-up no data on reproductive toxicology were available.
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| ID | Title | Description |
|---|---|---|
| FG000 | BI 1467335 10 mg (Low Dose) | Participants were orally administered 20 ml solution containing 10 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
| FG001 | BI 1467335 15 mg (Medium Dose) | Participants were orally administered 30 ml solution containing 15 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
| FG002 | BI 1467335 20 mg (High Dose) | Participants were orally administered 40 ml solution containing 20 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
| FG003 | Placebo | Participants were orally administered 40 ml solution containing 20 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated Set (TS): All participants who received at least 1 dose of trial medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | BI 1467335 10 mg (Low Dose) | Participants were orally administered 20 ml solution containing 10 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
| BG001 | BI 1467335 15 mg (Medium Dose) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | TS |
| 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 | Number of Subjects With Investigator Defined Drug-related Adverse Events | Number of subjects with investigator defined drug-related adverse events (AEs) is reported. | Treated set (TS): All participants who received at least 1 dose of trial medication. | Posted | Count of Participants | Participants | From first day of study drug administration until 20 days after last dose of study drug administration, up to 48 days. |
|
From first day of study drug administration until 20 days after last dose of study drug administration, up to 48 days.
Treated set (TS): All participants who received at least 1 dose of trial medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants were orally administered 40 ml solution containing 20 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear discomfort | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 5, 2016 | May 11, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 29, 2017 | May 11, 2021 | SAP_001.pdf |
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| Placebo |
| Drug |
|
| AUC0-24 |
AUC0-24 is the area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to 24 hours after administration of the first dose. |
| 0:00 hour (h) (within 30 minutes prior to dosing) and 0:15 h, 0:30 h, 0:45 h, 1:00 h, 1:30 h, 2:00 h, 3:00 h, 4:00 h, 6:00 h, 8:00 h, 10:00 h, 12:00 h and 24:00 h after drug administration on Day 1. |
| Cmax,28 | Cmax,28 is the maximum measured concentration of BI 1467335 in plasma following administration of the 28th dose. | 648:00 hours (h) (within 30 minutes prior to dosing) and 648:15 h, 648:30 h, 648:45 h, 649:00h, 649:30 h, 650:00 h, 651:00 h, 652:00 h, 654:00 h, 656:00 h, 658:00 h, 660:00 h, 672:00 h after first drug administration on Day 1. |
| AUC0-24,28 | AUC0-24,28 is the area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to 24 hours after administration of the 28th dose. | 648:00 hours (h) (within 30 minutes prior to dosing) and 648:15 h, 648:30 h, 648:45 h, 649:00 h, 649:30 h, 650:00 h, 651:00 h, 652:00 h, 654:00 h, 656:00 h, 658:00 h, 660:00 h and 672:00 h after first drug administration on Day 1. |
| Withdrawn due laboratory reason concerning neutrophils in agreement with the sponsor |
|
Participants were orally administered 30 ml solution containing 15 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
| BG002 | BI 1467335 20 mg (High Dose) | Participants were orally administered 40 ml solution containing 20 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
| BG003 | Placebo | Participants were orally administered 40 ml solution containing 20 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
| BG004 | Total | Total of all reporting groups |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | TS | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | TS | Count of Participants | Participants |
|
| Race (NIH/OMB) | TS | Count of Participants | Participants |
|
Participants were orally administered 30 ml solution containing 15 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h).
| OG002 | BI 1467335 20 mg (High Dose) | Participants were orally administered 40 ml solution containing 20 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
| OG003 | Placebo | Participants were orally administered 40 ml solution containing 20 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). |
|
|
| Secondary | Cmax | Cmax is the maximum measured concentration of BI 1467335 in plasma after administration of the first dose. | Pharmacokinetic parameter analysis set (PKS): All participants of the TS who provided at least 1 pharmacokinetic (PK) parameter that was not excluded due to relevant protocol violations or due to PK non-evaluability. Participants of the "Placebo" arm were not included in the analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomol/Liter (nmol/L) | 0:00 hour (h) (within 30 minutes prior to dosing) and 0:15 h, 0:30 h, 0:45 h, 1:00 h, 1:30 h, 2:00 h, 3:00 h, 4:00 h, 6:00 h, 8:00 h, 10:00 h, 12:00 h and 24:00 h after drug administration on Day 1. |
|
|
|
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| Secondary | AUC0-24 | AUC0-24 is the area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to 24 hours after administration of the first dose. | Pharmacokinetic parameter analysis set (PKS): All participants of the TS who provided at least 1 pharmacokinetic (PK) parameter that was not excluded due to relevant protocol violations or due to PK non-evaluability. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomol*hour/Liter (nmol*h/L) | 0:00 hour (h) (within 30 minutes prior to dosing) and 0:15 h, 0:30 h, 0:45 h, 1:00 h, 1:30 h, 2:00 h, 3:00 h, 4:00 h, 6:00 h, 8:00 h, 10:00 h, 12:00 h and 24:00 h after drug administration on Day 1. |
|
|
|
|
| Secondary | Cmax,28 | Cmax,28 is the maximum measured concentration of BI 1467335 in plasma following administration of the 28th dose. | Pharmacokinetic parameter analysis set (PKS): All participants of the TS who provided at least 1 pharmacokinetic (PK) parameter that was not excluded due to relevant protocol violations or due to PK non-evaluability. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomol/Liter (nmol/L) | 648:00 hours (h) (within 30 minutes prior to dosing) and 648:15 h, 648:30 h, 648:45 h, 649:00h, 649:30 h, 650:00 h, 651:00 h, 652:00 h, 654:00 h, 656:00 h, 658:00 h, 660:00 h, 672:00 h after first drug administration on Day 1. |
|
|
|
|
| Secondary | AUC0-24,28 | AUC0-24,28 is the area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to 24 hours after administration of the 28th dose. | Pharmacokinetic parameter analysis set (PKS): All participants of the TS who provided at least 1 pharmacokinetic (PK) parameter that was not excluded due to relevant protocol violations or due to PK non-evaluability. Participants of the "Placebo" arm were excluded from the analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomol*hour/Liter (nmol*h/L) | 648:00 hours (h) (within 30 minutes prior to dosing) and 648:15 h, 648:30 h, 648:45 h, 649:00 h, 649:30 h, 650:00 h, 651:00 h, 652:00 h, 654:00 h, 656:00 h, 658:00 h, 660:00 h and 672:00 h after first drug administration on Day 1. |
|
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| 7 |
| 9 |
| EG001 | BI 1467335 10 mg (Low Dose) | Participants were orally administered 20 ml solution containing 10 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). | 0 | 9 | 0 | 9 | 4 | 9 |
| EG002 | BI 1467335 15 mg (Medium Dose) | Participants were orally administered 30 ml solution containing 15 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). | 0 | 9 | 0 | 9 | 8 | 9 |
| EG003 | BI 1467335 20 mg (High Dose) | Participants were orally administered 40 ml solution containing 20 mg of BI 1467335: (0.5 mg/ml) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). | 0 | 9 | 0 | 9 | 7 | 9 |
| Eyelid oedema | Eye disorders | MedDRA 20.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Aphthous ulcer | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Vessel puncture site haematoma | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Vessel puncture site pain | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
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| Facial bones fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
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| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Apathy | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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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.
Standard Error of the mean is actually Standard Error of the slope. Based on the estimate for slope parameter (β), a 2-sided 95% CI for the slope was computed. Perfect dose proportionality would correspond to a slope of 1.
Standard Error of the mean is actually Standard Error of the slope. Based on the estimate for slope parameter (β), a 2-sided 95% CI for the slope was computed. Perfect dose proportionality would correspond to a slope of 1.
Standard Error of the mean is actually Standard Error of the slope. Based on the estimate for slope parameter (β), a 2-sided 95% CI for the slope was computed. Perfect dose proportionality would correspond to a slope of 1.
Standard Error of the mean is actually Standard Error of the slope. Based on the estimate for slope parameter (β), a 2-sided 95% CI for the slope was computed. Perfect dose proportionality would correspond to a slope of 1.