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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-510461-10-00 | Registry Identifier | CTIS | |
| U1111-1303-9187 | Registry Identifier | WHO International Clinical Trials Registry Platform (ICTRP) |
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The main objective of this trial is to investigate the effect of multiple oral doses of BI 1569912 on the pharmacokinetics of a single oral dose of repaglinide, midazolam and bupropion (i.e. sensitive CYP2C8, CYP3A4 and CYP2B6 substrates).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Reference treatment (R), then test treatment (T) | Experimental | Reference Treatment (R): On the morning of Day (D) 1, healthy participants received a single tablet of 0.5 milligrams (mg) of repaglinide orally. On the morning of D2, participants took a single dose of 2 mg of midazolam solution for injection orally. On the morning of D3, participants received orally a single extended-release tablet of 150 mg of bupropion. All medications were administered after an overnight fast of at least 10 hours. Test Treatment (T): Healthy participants received in the morning, for 21 days (D-14 to D7), the intended BI 1569912 daily dose. On the morning of D1, participants took after the administration of BI 1569912, a single tablet of 0.5 mg of repaglinide orally. On the morning of D2, participants took, after the administration of BI 1569912, a single dose of 2 mg of midazolam solution for injection orally. On the morning of D3, participants received orally a single extended-release tablet of 150 mg of bupropion after BI 1569912. No washout period occurred. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 1569912 | Drug | Intended dose of BI 1569912 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of Repaglinide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | This outcome measured the area under the concentration-time curve of repaglinide in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before repaglinide administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
| Area Under Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | This outcome measured the area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before midazolam administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
| Area Under the Concentration-time Curve of S-bupropion in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | This outcome measured the area under the concentration-time curve of chiral form S-bupropion in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞), when bupropion was administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of Repaglinide in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | This outcome measured the area under the concentration-time curve of repaglinide in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. |
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Inclusion Criteria:
Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, standardized mental and neurological assessment, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests without clinically significant abnormalities
Age of 18 to 55 years (inclusive)
Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
Either male subjects or female subjects who meet the following criteria requiring highly effective contraception from at least 30 days before the first administration of trial medication until 30 days after trial completion:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| SGS Life Science Services - Clinical Research | Edegem | 2650 | Belgium |
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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. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).
For more details refer to:
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All participants were screened for eligibility prior to participation in the trial. Participants attended a specialist site which ensured that they strictly met all inclusion and none of the exclusion criteria. Participants were not to be allocated to a treatment group if any of the entry criteria were violated.
This was a non-randomized, open-label, 2-period trial in healthy male and female participants in order to test the influence of multiple doses of BI 1569912 on the pharmacokinetics of repaglinide, midazolam, and bupropion (sensitive CYP2C8, CYP3A4 and CYP2B6 substrates).
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| ID | Title | Description |
|---|---|---|
| FG000 | Reference Treatment (R), Then Test Treatment (T) | Reference (R) Treatment: On the morning of Day 1, healthy participants received a single tablet of 0.5 milligrams (mg) of repaglinide orally. On the morning of Day 2, participants took a single dose of 2 mg of midazolam solution for injection orally. On the morning of Day 3, participants received orally a single extended-release tablet of 150 mg of bupropion. All medications were administered after an overnight fast of at least 10 hours. Test Treatment (T): Healthy participants received in the morning, for 21 days (Day -14 to Day 7), the intended BI 1569912 daily dose, orally after an overnight fast of at least 10 hours. On the morning of Day 1, participants received after the administration of BI 1569912, a single tablet of 0.5 mg of repaglinide orally. On the morning of Day 2, participants took, after the administration of BI 1569912, a single dose of 2 mg of midazolam solution for injection orally. On the morning of Day 3, participants received orally a single extended-release tablet of 150 mg of bupropion after BI 1569912. No washout period occurred between treatment periods. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Reference (R) treatment period |
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| Test (T) treatment period |
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Treated set (TS): all participants who were treated with at least one dose of trial drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Reference Treatment (R), Then Test Treatment (T) | Reference (R) Treatment: On the morning of Day 1, healthy participants received a single tablet of 0.5 milligrams (mg) of repaglinide orally. On the morning of Day 2, participants took a single dose of 2 mg of midazolam solution for injection orally. On the morning of Day 3, participants received orally a single extended-release tablet of 150 mg of bupropion. All medications were administered after an overnight fast of at least 10 hours. Test Treatment (T): Healthy participants received in the morning, for 21 days (Day -14 to Day 7), the intended BI 1569912 daily dose, orally after an overnight fast of at least 10 hours. On the morning of Day 1, participants received after the administration of BI 1569912, a single tablet of 0.5 mg of repaglinide orally. On the morning of Day 2, participants took, after the administration of BI 1569912, a single dose of 2 mg of midazolam solution for injection orally. On the morning of Day 3, participants received orally a single extended-release tablet of 150 mg of bupropion after BI 1569912. No washout period occurred between treatment periods. |
| 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 | Area Under the Concentration-time Curve of Repaglinide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | This outcome measured the area under the concentration-time curve of repaglinide in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. | Posted | Geometric Least Squares Mean | Standard Error | hour*picomole/liter | Within 3 hours (h) before repaglinide administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
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All-cause mortality: From first drug administration until individual end of study. Up to 39 days. Adverse event reporting: From first drug administration until last drug administration, plus residual effect period. Up to 15.5 days.
Treated set (TS): all participants who were treated with at least one dose of trial drug.
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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 | Repaglinide 0.5 mg (R1) | Healthy participants received a single tablet of 0.5 milligrams (mg) of repaglinide orally on the morning of Day 1 of the reference treatment period, after an overnight fast of at least 10 hours. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vision blurred | Eye disorders | MedDRA 27.0 | 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 | Feb 15, 2024 | Apr 28, 2026 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 10, 2024 | Apr 28, 2026 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C072379 | repaglinide |
| D008874 | Midazolam |
| D016642 | Bupropion |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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Patients cross over from test treatment (T) to reference treatment (R) (two periods, fixed sequence).
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| Repaglinide |
| Drug |
0.5 mg tablet |
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| Midazolam | Drug | 2 mg solution for injection |
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| Bupropion | Drug | 150 mg extended-release tablet |
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| Area Under the Concentration-time Curve of Total Bupropion in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | This outcome measured the area under the concentration-time curve of total bupropion in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞), when bupropion was administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
| Within 3 hours (h) before repaglinide administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
| Maximum Measured Concentration of Repaglinide in Plasma (Cmax) | This outcome measured maximum measured concentration of repaglinide in plasma (Cmax), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before repaglinide administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
| Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | This outcome measured the area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz), when administered alone or co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before midazolam administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
| Maximum Measured Concentration of Midazolam in Plasma (Cmax) | This outcome measured maximum measured concentration of midazolam in plasma (Cmax), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before midazolam administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
| Area Under the Concentration-time Curve of S-bupropion in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | This outcome measured the area under the concentration-time curve of the chiral form S-bupropion in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz), when bupropion was administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
| Maximum Measured Concentration of S-bupropion in Plasma (Cmax) | This outcome measured maximum measured concentration of the chiral form S-bupropion in plasma (Cmax), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
| Area Under the Concentration-time Curve of Total Bupropion in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | This outcome measured the area under the concentration-time curve of total bupropion in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz), when bupropion was administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
| Maximum Measured Concentration of Total Bupropion in Plasma (Cmax) | This outcome measured maximum measured concentration of total bupropion in plasma (Cmax), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Description |
|---|
| OG000 | Repaglinide 0.5 mg (R1) | Healthy participants received a single tablet of 0.5 milligrams (mg) of repaglinide orally on the morning of Day 1 of the Reference (R) treatment period, after an overnight fast of at least 10 hours. |
| OG001 | Repaglinide 0.5 mg + BI 1569912 (T1) | Healthy participants received after the administration of BI 1569912 dose, a single tablet of 0.5 mg of repaglinide orally on the morning of Day 1 of the Test (T) treatment period. |
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| Primary | Area Under Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | This outcome measured the area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. One participant discontinued treatment due to an adverse event during the reference treatment period and only received repaglinide. | Posted | Geometric Least Squares Mean | Standard Error | hour*picomole/liter | Within 3 hours (h) before midazolam administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
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| Secondary | Area Under the Concentration-time Curve of Repaglinide in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | This outcome measured the area under the concentration-time curve of repaglinide in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. | Posted | Geometric Least Squares Mean | Standard Error | hour*picomole/liter | Within 3 hours (h) before repaglinide administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
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| Primary | Area Under the Concentration-time Curve of S-bupropion in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | This outcome measured the area under the concentration-time curve of chiral form S-bupropion in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞), when bupropion was administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. One participant discontinued treatment due to an adverse event during the reference treatment period and only received repaglinide. | Posted | Geometric Least Squares Mean | Standard Error | hour*nanomole/liter | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
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| Secondary | Maximum Measured Concentration of Repaglinide in Plasma (Cmax) | This outcome measured maximum measured concentration of repaglinide in plasma (Cmax), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. | Posted | Geometric Least Squares Mean | Standard Error | picomole/liter | Within 3 hours (h) before repaglinide administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
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| Secondary | Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | This outcome measured the area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz), when administered alone or co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. One participant discontinued treatment due to an adverse event during the reference treatment period and only received repaglinide. | Posted | Geometric Least Squares Mean | Standard Error | hour*picomole/liter | Within 3 hours (h) before midazolam administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
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| Secondary | Maximum Measured Concentration of Midazolam in Plasma (Cmax) | This outcome measured maximum measured concentration of midazolam in plasma (Cmax), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. One participant discontinued treatment due to an adverse event during the reference treatment period and only received repaglinide. | Posted | Geometric Least Squares Mean | Standard Error | picomole/liter | Within 3 hours (h) before midazolam administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h thereafter. |
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| Primary | Area Under the Concentration-time Curve of Total Bupropion in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | This outcome measured the area under the concentration-time curve of total bupropion in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞), when bupropion was administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. One participant discontinued treatment due to an adverse event during the reference treatment period and only received repaglinide. | Posted | Geometric Least Squares Mean | Standard Error | hour*nanomole/liter | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
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| Secondary | Area Under the Concentration-time Curve of S-bupropion in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | This outcome measured the area under the concentration-time curve of the chiral form S-bupropion in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz), when bupropion was administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. One participant discontinued treatment due to an adverse event during the reference treatment period and only received repaglinide. | Posted | Geometric Least Squares Mean | Standard Error | hour*nanomole/liter | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
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| Secondary | Maximum Measured Concentration of S-bupropion in Plasma (Cmax) | This outcome measured maximum measured concentration of the chiral form S-bupropion in plasma (Cmax), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. One participant discontinued treatment due to an adverse event during the reference treatment period and only received repaglinide. | Posted | Geometric Least Squares Mean | Standard Error | nanomole/liter | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
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| Secondary | Area Under the Concentration-time Curve of Total Bupropion in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | This outcome measured the area under the concentration-time curve of total bupropion in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz), when bupropion was administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. One participant discontinued treatment due to an adverse event during the reference treatment period and only received repaglinide. | Posted | Geometric Least Squares Mean | Standard Error | hour*nanomole/liter | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
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| Secondary | Maximum Measured Concentration of Total Bupropion in Plasma (Cmax) | This outcome measured maximum measured concentration of total bupropion in plasma (Cmax), when administered alone and when co-administered at BI 1569912 steady-state. The statistical model used was an analysis of variance (ANOVA) accounting for the following sources of variation: participant and treatment. The effect 'participant' was considered as random, whereas the effect 'treatment' was considered as fixed. | Pharmacokinetic (PK) parameter analysis set (PKS): all participants who were treated with at least one dose of trial drug and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. One participant discontinued treatment due to an adverse event during the reference treatment period and only received repaglinide. | Posted | Geometric Least Squares Mean | Standard Error | nanomole/liter | Within 3 hours (h) before bupropion administration and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 h thereafter. |
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| 0 |
| 18 |
| 0 |
| 18 |
| 1 |
| 18 |
| EG001 | Midazolam 2 mg (R2) | Healthy participants received a single dose of 2 mg of midazolam solution for injection orally on the morning of Day 2 of the reference period (R), after an overnight fast of at least 10 hours. | 0 | 17 | 0 | 17 | 5 | 17 |
| EG002 | Bupropion 150 mg (R3) | Healthy participants received a single extended-release tablet of 150 mg of bupropion orally on the morning of Day 3 of the reference period (R), after an overnight fast of at least 10 hours. | 0 | 17 | 0 | 17 | 3 | 17 |
| EG003 | BI 1569912 | Healthy participants received in the morning, for 14 days (Day -14 to Day -1 of the test treatment period), the intended dose of BI 1569912, orally after an overnight fast of at least 10 hours. | 0 | 17 | 0 | 17 | 12 | 17 |
| EG004 | Repaglinide 0.5 mg + BI 1569912 (T1) | Healthy participants received after the administration of the intended dose of BI 1569912, a single tablet of 0.5 mg of repaglinide orally on the morning of Day 1 of the test treatment period. | 0 | 17 | 0 | 17 | 0 | 17 |
| EG005 | Midazolam 2 mg + BI 1569912 (T2) | Healthy participants received after the administration of the intended dose of BI 1569912, a single dose of 2 mg of midazolam solution for injection orally on the morning of Day 2 of the test treatment period (T). | 0 | 17 | 0 | 17 | 2 | 17 |
| EG006 | Bupropion 150 mg + BI 1569912 (T3) | Healthy participants received after the administration of the intended dose of BI 1569912, a single extended-release tablet of 150 mg of bupropion orally on the morning of Day 3 of the test treatment period (T). | 0 | 17 | 0 | 17 | 6 | 17 |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Application site rash | General disorders | MedDRA 27.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 27.0 | Systematic Assessment |
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| Early satiety | General disorders | MedDRA 27.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 27.0 | Systematic Assessment |
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| Muscle strain | Injury, poisoning and procedural complications | MedDRA 27.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
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| Disturbance in attention | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
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| Abnormal dreams | Psychiatric disorders | MedDRA 27.0 | Systematic Assessment |
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| Nightmare | Psychiatric disorders | MedDRA 27.0 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 27.0 | Systematic Assessment |
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| Heavy menstrual bleeding | Reproductive system and breast disorders | MedDRA 27.0 | Systematic Assessment |
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| Menstruation irregular | Reproductive system and breast disorders | MedDRA 27.0 | Systematic Assessment |
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| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 27.0 | 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.
| D006571 | Heterocyclic Compounds |
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |