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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-004238-13 | EudraCT Number |
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The primary objective of this trial is to investigate the safety and tolerability of BI 1323495 in healthy subjects following bid oral administration of multiple rising doses, each over an 11 day treatment period.
Secondary objectives are the exploration of the pharmacokinetics (PK) including dose proportionality (only for Part 1) as well as attainment of steady state. This includes exploration of a therapeutic exposure range, a range not adequately achieved in the single-rising dose trial 1405-0001.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 10 mg BI 1323495 bid EM | Experimental |
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| 10 mg BI 1323495 bid PM | Experimental |
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| 30 mg BI 1323495 bid EM | Experimental |
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| 30 mg BI 1323495 bid PM | Experimental |
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| 70 mg BI 1323495 bid + Midazolam EM | Experimental |
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| 120 mg BI 1323495 bid + Midazolam EM | Experimental |
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| 120 mg BI 1323495 qd EM | Experimental |
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| 150 mg BI 1323495 bid + Midazolam EM |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 1323495 | Drug | Tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Treatment-emergent Drug-related Adverse Events (AEs) | Percentage of participants with treatment-emergent drug-related Adverse Events (AEs) is reported. Percentages are calculated using total number of subjects per treatment as the denominator. | Midazolam alone: From administration of midazolam on Day -1 until first administration of BI 1323495 on Day 1, up to 24 hours. All others: From first administration until 7 days after the last administration of BI 1323495, up to 18 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1323495 in Plasma Over a Time Interval of 12 h After Administration of the First Dose (AUC0-12) | Area under the concentration-time curve of BI 1323495 in plasma over a time interval of 12 h after administration of the first dose (AUC0-12) is reported. | Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, and 12h after the first administration of BI 1323495 on Day 1. |
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Inclusion criteria:
For Part II: Subjects genotyped as UGT2B17 poor metabolizers, i.e., carrying no functional allele of the UGT2B17 gene (*2/*2)
-Male or female subjects:
Exclusion criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fraunhofer ITEM | Hanover | 30625 | Germany |
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| Label | URL |
|---|---|
| Related Info | View source |
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Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:
For more details refer to:
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All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
This was a trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising oral doses of BI 1323495 versus placebo in healthy subjects, including an investigation of drug-drug interaction with microdose midazolam (double-blind, randomised, placebo-controlled [within dose groups] trial).
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo/Placebo + Midazolam | This arm comprises placebo only treated participants and those participants who received placebo + midazolam. Placebo only treated participants were administered film-coated tablets of placebo matching BI 1323495 dosage and participants who received placebo + midazolam were administered film-coated tablets of placebo matching BI 1323495 dosage + a single daily dose of 1.5 milliliter (mL) of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast on Day -1 and on Day 11. |
| FG001 | 10 mg BI 1323495 Bid EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 10 milligram (mg) of BI 1323495 orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| FG002 | 10 mg BI 1323495 Bid PM | Participants carrying no functional allele of the UGT2B17 gene (poor metabolisers (PM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 10 milligram (mg) of BI 1323495 orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| FG003 | 30 mg BI 1323495 Bid EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) three film-coated tablets of 10 milligram (mg) of BI 1323495 (total dosage=30 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| FG004 | 30 mg BI 1323495 Bid PM | Participants carrying no functional allele of the UGT2B17 gene (poor metabolisers (PM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) three film-coated tablets of 10 milligram (mg) of BI 1323495 (total dosage = 30 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| FG005 | 70 mg BI 1323495 Bid + Midazolam EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and one film-coated tablet of 50 mg of BI 1323495 (total dosage=70 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. |
| FG006 | 120 mg BI 1323495 Bid + Midazolam EM | Participants with at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and two film-coated tablets of 50 mg of BI 1323495 (total dosage=120 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. |
| FG007 | 120 mg BI 1323495 qd EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and two film-coated tablets of 50 mg of BI 1323495 (total dosage=120 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| FG008 | 150 mg BI 1323495 Bid + Midazolam EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 150 milligram (mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Treated Set (TS): The treated set included all subjects who were randomised and treated with at least 1 dose of trial drug. The treatment assignment was determined based on the first treatment the subjects received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo/Placebo + Midazolam | This arm comprises placebo only treated participants and those participants who received placebo + midazolam. Placebo only treated participants were administered film-coated tablets of placebo matching BI 1323495 dosage and participants who received placebo + midazolam were administered film-coated tablets of placebo matching BI 1323495 dosage + a single daily dose of 1.5 milliliter (mL) of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast on Day -1 and on Day 11. |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Percentage of Participants With Treatment-emergent Drug-related Adverse Events (AEs) | Percentage of participants with treatment-emergent drug-related Adverse Events (AEs) is reported. Percentages are calculated using total number of subjects per treatment as the denominator. | Treated Set (TS): The treated set included all subjects who were randomised and treated with at least 1 dose of trial drug. The treatment assignment was determined based on the first treatment the subjects received. Midazolam alone arm consisted of all subjects of the arms "70 mg BI 1323495 bid+Midazolam EM", "120 mg BI 1323495 bid+Midazolam EM", "150 mg BI 1323495 bid+ Midazolam EM" and 9 subjects of the arm "Placebo/Placebo+Midazolam" which were treated with midazolam on Day -1 of the trial. | Posted | Number | percentage of participants | Midazolam alone: From administration of midazolam on Day -1 until first administration of BI 1323495 on Day 1, up to 24 hours. All others: From first administration until 7 days after the last administration of BI 1323495, up to 18 days. |
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Midazolam alone: From administration of midazolam on Day -1 until first administration of BI 1323495 on Day 1, up to 24 hours. All others: From first administration until 7 days after the last administration of BI 1323495, up to 18 days.
Treated Set (TS): The treated set included all subjects who were randomised and treated with at least 1 dose of trial drug. The treatment assignment was determined based on the first treatment the subjects received. Midazolam alone arm consisted of all subjects of the arms "70 mg BI 1323495 bid+Midazolam EM", "120 mg BI 1323495 bid+Midazolam EM", "150 mg BI 1323495 bid+ Midazolam EM" and 9 subjects of the arm "Placebo/Placebo+Midazolam" which were treated with midazolam on Day -1 of the trial.
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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/Placebo + Midazolam | This arm comprises placebo only treated participants and those participants who received placebo + midazolam. Placebo only treated participants were administered film-coated tablets of placebo matching BI 1323495 dosage and participants who received placebo + midazolam were administered film-coated tablets of placebo matching BI 1323495 dosage + a single daily dose of 1.5 milliliter (mL) of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast on Day -1 and on Day 11. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 23.1 | 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 | Dec 10, 2020 | Jun 29, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 8, 2021 | Jun 29, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Experimental |
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| Placebo/Placebo+ Midazolam | Experimental |
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| Placebo | Drug | Tablet |
|
| Midazolam | Drug | Oral administration |
|
| Only for Once Daily (qd) Dosing Group: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over a Uniform Dosing Interval of 24 h After Administration of the First Dose (AUC0-24) | Area under the concentration-time curve of BI 1323495 in plasma over a uniform dosing interval of 24 h after administration of the first dose (AUC0-24) for the once daily (qd) dosing group is reported. | Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24 h after administration of BI 1323495 on Day 1. |
| Maximum Measured Concentration of BI 1323495 in Plasma After the First Dose (Cmax) | Maximum measured concentration of BI 1323495 in plasma after the first dose (Cmax) is reported. | Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the first administration of BI 1323495 on Day 1. * Applicable only for the 120 mg BI 1323495 qd EM arm. |
| Area Under the Concentration-time Curve of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | Area under the concentration-time curve of BI 1323495 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) is reported. The dosing interval τ is not the same for all groups. The dosing interval is 12 hours (h) for the dose groups with a twice daily (bid) BI 1323495 administration and 24 h for the dose group with a once daily (qd) BI 1323495 administration. | Within 3 hours before and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the last administration of BI 1323495 on Day 11. * Applicable only for the 120 mg BI 1323495 qd EM arm. |
| Maximum Measured Concentration of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | Maximum measured concentration of BI 1323495 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) is reported. The dosing interval τ is not the same for all groups. The dosing interval is 12 hours (h) for the dose groups with a twice daily (bid) BI 1323495 administration and 24 h for the dose group with a once daily (qd) BI 1323495 administration. | Within 3 hours before and 20 min, 40 min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the last drug administration of BI 1323495 on Day 11. * Applicable only for the 120 mg BI 1323495 qd EM arm. |
| BG001 | 10 mg BI 1323495 Bid EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 10 milligram (mg) of BI 1323495 orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| BG002 | 10 mg BI 1323495 Bid PM | Participants carrying no functional allele of the UGT2B17 gene (poor metabolisers (PM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 10 milligram (mg) of BI 1323495 orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| BG003 | 30 mg BI 1323495 Bid EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) three film-coated tablets of 10 milligram (mg) of BI 1323495 (total dosage=30 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| BG004 | 30 mg BI 1323495 Bid PM | Participants carrying no functional allele of the UGT2B17 gene (poor metabolisers (PM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) three film-coated tablets of 10 milligram (mg) of BI 1323495 (total dosage = 30 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| BG005 | 70 mg BI 1323495 Bid + Midazolam EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and one film-coated tablet of 50 mg of BI 1323495 (total dosage=70 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. |
| BG006 | 120 mg BI 1323495 Bid + Midazolam EM | Participants with at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and two film-coated tablets of 50 mg of BI 1323495 (total dosage=120 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. |
| BG007 | 120 mg BI 1323495 qd EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and two film-coated tablets of 50 mg of BI 1323495 (total dosage=120 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| BG008 | 150 mg BI 1323495 Bid + Midazolam EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 150 milligram (mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. |
| BG009 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG000 |
| Placebo/Placebo+ Midazolam |
This arm comprises placebo only treated participants and those participants who received placebo + midazolam. Placebo only treated participants were administered film-coated tablets of placebo matching BI 1323495 dosage and participants who received placebo + midazolam were administered film-coated tablets of placebo matching BI 1323495 dosage + a single dose of 1.5 ml of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast on Day -1 and on Day 11. |
| OG001 | Midazolam Alone | This arm consisted of all participants of the arms "70 mg BI 1323495 bid + Midazolam EM", "120 mg BI 1323495 bid + Midazolam EM", "150 mg BI 1323495 bid + Midazolam EM" and 9 subjects of the arm "Placebo/Placebo + Midazolam" which were administered midazolam on Day -1 of the trial. The duration of this analysis phase was approximately 1 day (from Day -1 to first administration of BI 1323495 on Day 1). |
| OG002 | 10 mg BI 1323495 Bid EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 10 milligram (mg) of BI 1323495 orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| OG003 | 10 mg BI 1323495 Bid PM | Participants carrying no functional allele of the UGT2B17 gene (poor metabolisers (PM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 10 milligram (mg) of BI 1323495 orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| OG004 | 30 mg BI 1323495 Bid EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) three film-coated tablets of 10 milligram (mg) of BI 1323495 (total dosage=30 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| OG005 | 30 mg BI 1323495 Bid PM | Participants carrying no functional allele of the UGT2B17 gene (poor metabolisers (PM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) three film-coated tablets of 10 milligram (mg) of BI 1323495 (total dosage = 30 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| OG006 | 70 mg BI 1323495 Bid + Midazolam EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and one film-coated tablet of 50 mg of BI 1323495 (total dosage=70 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. |
| OG007 | 120 mg BI 1323495 Bid + Midazolam EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and two film-coated tablets of 50 mg of BI 1323495 (total dosage=120 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. |
| OG008 | 120 mg BI 1323495 qd EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and two film-coated tablets of 50 mg of BI 1323495 (total dosage=120 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. |
| OG009 | 150 mg BI 1323495 Bid + Midazolam EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 150 milligram (mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. |
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| Secondary | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over a Time Interval of 12 h After Administration of the First Dose (AUC0-12) | Area under the concentration-time curve of BI 1323495 in plasma over a time interval of 12 h after administration of the first dose (AUC0-12) is reported. | Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he/she contributed to only 1 PK parameter value for 1 period to the statistical assessment. Only participants with evaluable results for this PK parameter are reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours *nanomol/Liter (h*nmol/L) | Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, and 12h after the first administration of BI 1323495 on Day 1. |
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| Secondary | Only for Once Daily (qd) Dosing Group: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over a Uniform Dosing Interval of 24 h After Administration of the First Dose (AUC0-24) | Area under the concentration-time curve of BI 1323495 in plasma over a uniform dosing interval of 24 h after administration of the first dose (AUC0-24) for the once daily (qd) dosing group is reported. | Pharmacokinetic (PK) parameter analysis set (PKS) of 120 mg BI qd EM arm: This set included all treated subjects of 120 mg BI 1323495 qd EM arm who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS of arm, even if he/she contributed to only 1 PK parameter value for 1 period to the statistical assessment. Only participants with evaluable results are reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours *nanomol/Liter (h*nmol/L) | Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24 h after administration of BI 1323495 on Day 1. |
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| Secondary | Maximum Measured Concentration of BI 1323495 in Plasma After the First Dose (Cmax) | Maximum measured concentration of BI 1323495 in plasma after the first dose (Cmax) is reported. | Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he/she contributed to only 1 PK parameter value for 1 period to the statistical assessment. Only participants with evaluable results of this PK parameter are reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomol/Liter (nmol/L) | Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the first administration of BI 1323495 on Day 1. * Applicable only for the 120 mg BI 1323495 qd EM arm. |
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| Secondary | Area Under the Concentration-time Curve of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | Area under the concentration-time curve of BI 1323495 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) is reported. The dosing interval τ is not the same for all groups. The dosing interval is 12 hours (h) for the dose groups with a twice daily (bid) BI 1323495 administration and 24 h for the dose group with a once daily (qd) BI 1323495 administration. | Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he/she contributed to only 1 PK parameter value for 1 period to the statistical assessment. Only participants with evaluable results for this PK parameter are reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours *nanomol/Liter (hnmol/L) | Within 3 hours before and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the last administration of BI 1323495 on Day 11. * Applicable only for the 120 mg BI 1323495 qd EM arm. |
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| Secondary | Maximum Measured Concentration of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | Maximum measured concentration of BI 1323495 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) is reported. The dosing interval τ is not the same for all groups. The dosing interval is 12 hours (h) for the dose groups with a twice daily (bid) BI 1323495 administration and 24 h for the dose group with a once daily (qd) BI 1323495 administration. | Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he/she contributed to only 1 PK parameter value for 1 period to the statistical assessment. Only participants with evaluable results for this PK parameter are reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomol/liter (nmol/L) | Within 3 hours before and 20 min, 40 min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the last drug administration of BI 1323495 on Day 11. * Applicable only for the 120 mg BI 1323495 qd EM arm. |
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| 0 |
| 22 |
| 0 |
| 22 |
| 9 |
| 22 |
| EG001 | Midazolam Alone | This arm consisted of all participants of the arms "70 mg BI 1323495 bid + Midazolam EM", "120 mg BI 1323495 bid + Midazolam EM", "150 mg BI 1323495 bid + Midazolam EM" and 9 subjects of the arm "Placebo/Placebo + Midazolam" which were administered midazolam on Day -1 of the trial. The duration of this analysis phase was approximately 1 day (from Day -1 to first administration of BI 1323495 on Day 1). | 0 | 36 | 0 | 36 | 2 | 36 |
| EG002 | 10 mg BI 1323495 Bid EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 10 milligram (mg) of BI 1323495 orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. | 0 | 9 | 0 | 9 | 6 | 9 |
| EG003 | 10 mg BI 1323495 Bid PM | Participants carrying no functional allele of the UGT2B17 gene (poor metabolisers (PM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 10 milligram (mg) of BI 1323495 orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. | 0 | 5 | 0 | 5 | 3 | 5 |
| EG004 | 30 mg BI 1323495 Bid EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) three film-coated tablets of 10 milligram (mg) of BI 1323495 (total dosage=30 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. | 0 | 9 | 0 | 9 | 8 | 9 |
| EG005 | 30 mg BI 1323495 Bid PM | Participants carrying no functional allele of the UGT2B17 gene (poor metabolisers (PM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) three film-coated tablets of 10 milligram (mg) of BI 1323495 (total dosage = 30 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG006 | 70 mg BI 1323495 Bid + Midazolam EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and one film-coated tablet of 50 mg of BI 1323495 (total dosage=70 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single dose of 1.5 ml of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. | 0 | 9 | 0 | 9 | 6 | 9 |
| EG007 | 120 mg BI 1323495 Bid + Midazolam EM | Participants with at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and two film-coated tablets of 50 mg of BI 1323495 (total dosage=120 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. | 0 | 9 | 0 | 9 | 4 | 9 |
| EG008 | 120 mg BI 1323495 qd EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 11 once daily (qd) two film-coated tablets of 10 milligram (mg) and two film-coated tablets of 50 mg of BI 1323495 (total dosage=120 mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. | 0 | 9 | 0 | 9 | 6 | 9 |
| EG009 | 150 mg BI 1323495 Bid + Midazolam EM | Participants carrying at least one functional allele of the UGT2B17 gene (extensive metabolisers (EM)) were administered from Day 1 to Day 10 twice daily (bid) and on Day 11 once daily (qd) one film-coated tablet of 150 milligram (mg) orally with 240 milliliter (mL) of water within 30 minutes (min) of a meal. On Day -1 and on Day 11 participants were also administered a single daily dose of 1.5 mL of solution for injection of midazolam concentrated 50 microgram (ug)/mL (total dosage=75 ug) orally with 240 mL of water within 30 minutes after a standard breakfast. | 0 | 9 | 0 | 9 | 6 | 9 |
| Head discomfort | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Restless legs syndrome | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Tension headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Abdominal pain lower | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Limb injury | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA 23.1 | Systematic Assessment |
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| Electrocardiogram PR shortened | Investigations | MedDRA 23.1 | Systematic Assessment |
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| Electrocardiogram QT prolonged | Investigations | MedDRA 23.1 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Solar urticaria | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Bradyphrenia | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Laziness | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Hyperarousal | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Tension | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 23.1 | Systematic Assessment |
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| Ear discomfort | Ear and labyrinth disorders | MedDRA 23.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Tendon pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Photophobia | Eye disorders | MedDRA 23.1 | Systematic Assessment |
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| Food allergy | Immune system disorders | MedDRA 23.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 23.1 | 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.
| D006571 | Heterocyclic Compounds |