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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-510263-35-00 | Registry Identifier | CTIS | |
| U1111-1301-9035 | Registry Identifier | WHO International Clinical Trials Registry Platform (ICTRP) |
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The main objective of this trial is to assess the effect of multiple oral doses of zongertinib on the pharmacokinetics of midazolam, omeprazole and repaglinide.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Repaglinide+Midazolam+Omeprazole (Reference)/ Zongertinib+Repaglinide+Midazolam+Omeprazole (Test) | Experimental | Reference (Repaglinide + Midazolam + Omeprazole) In the reference treatment period (Period 1), participants received 0.5 mg repaglinide tablet (Day 1, after ≥10 h fast; Reference Treatment 1). On Day 2, they received 1 mg midazolam (0.5 mL oral solution) with 20 mg omeprazole tablet under the same fasting conditions (Reference Treatment 2). Test (Zongertinib + Repaglinide + Midazolam + Omeprazole) In the test treatment period (Period 2), participants received multiple once-daily doses of 120 mg zongertinib from Day 1 to Day 15. A single 0.5 mg repaglinide tablet was co-administered on Day 1 (Test Treatment 1) and Day 14 (Test Treatment 3), and a single dose of the probe drug cocktail containing 1 mg midazolam (0.5 mL oral solution) and 20 mg omeprazole tablet was co-administered on Day 2 (Test Treatment 2) and Day 15 (Test Treatment 4). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| zongertinib | Drug | Participants received 120 mg Zongertinib daily as two 60 mg tablets. |
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| Measure | Description | Time Frame |
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| Area Under the Concentration-time Curve of Repaglinide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC₀-∞) | The area under the concentration-time curve of repaglinide in plasma over the time interval from 0 extrapolated to infinity ((AUC0-∞) is reported. Period 1 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 14): ≤15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 2.5, 3-, 4-,6-, and 24-hours post-dose. | Samples were collected on Day 1 (Period 1), Day 1 (Period 2), and Day 14 (Period 2). See endpoint description for the full sampling schedule |
| Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC₀-∞) | The area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity ((AUC0-∞) is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
| Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC₀-∞) | The area under the concentration-time curve of omeprazole in plasma over the time interval from 0 extrapolated to infinity ((AUC0-∞) is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
| 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) | The area under the concentration-time curve of repaglinide in plasma over the time interval from 0 to the last quantifiable data poin is reported. Period 1 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 14): ≤15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 2.5, 3-, 4-,6-, and 24-hours post-dose. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Humanpharmakologisches Zentrum Biberach | Biberach | 88397 | Germany |
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| Label | URL |
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| 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 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 non-randomized, open-label, two-period, fixed-sequence trial evaluated the effect of multiple oral doses of zongertinib on the single-dose pharmacokinetics of midazolam, omeprazole, and repaglinide in healthy male subjects to assess potential drug-drug interactions.
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| ID | Title | Description |
|---|---|---|
| FG000 | Repaglinide+Midazolam+Omeprazole (Reference)/ Zongertinib+Repaglinide+Midazolam+Omeprazole (Test) | Reference (Repaglinide + Midazolam + Omeprazole) In the reference treatment period (Period 1), participants received 0.5 mg repaglinide tablet (Day 1, after ≥10 h fast; Reference Treatment 1). On Day 2, they received 1 mg midazolam (0.5 mL oral solution) with 20 mg omeprazole tablet under the same fasting conditions (Reference Treatment 2). Test (Zongertinib + Repaglinide + Midazolam + Omeprazole) In the test treatment period (Period 2), participants received multiple once-daily doses of 120 mg zongertinib from Day 1 to Day 15. A single 0.5 mg repaglinide tablet was co-administered on Day 1 (Test Treatment 1) and Day 14 (Test Treatment 3), and a single dose of the probe drug cocktail containing 1 mg midazolam (0.5 mL oral solution) and 20 mg omeprazole tablet was co-administered on Day 2 (Test Treatment 2) and Day 15 (Test Treatment 4). |
| Title | Milestones | Reasons Not Completed | ||||
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| Period 1 (Reference Period) (3 days) |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
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| Prot | Yes | No | No | Study Protocol | Jul 12, 2024 | Nov 4, 2025 |
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| midazolam | Drug | Participants received 1 mg Midazolam as 0.5 mL oral solution. |
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| omeprazole | Drug | Participants received 20 mg Omeprazole. |
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| repaglinide | Drug | Participants received a 0.5 mg Repaglinide. |
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| Maximum Measured Concentration of Repaglinide in Plasma (Cmax) | The maximum measured concentration of repaglinide in plasma is reported. Period 1 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 14): ≤15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 2.5, 3-, 4-,6-, and 24-hours post-dose. | Samples were collected on Day 1 (Period 1), Day 1 (Period 2), and Day 14 (Period 2). See endpoint description for the full sampling schedule |
| Maximum Measured Concentration of Midazolam in Plasma (Cmax) | The maximum measured concentration of midazolam in plasma is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
| Maximum Measured Concentration of Omeprazole in Plasma (Cmax) | The maximum measured concentration of omeprazole in plasma is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
| Samples were collected on Day 1 (Period 1), Day 1 (Period 2), and Day 14 (Period 2). See endpoint description for the full sampling schedule |
| Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | The area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
| Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | The area under the concentration-time curve of omeprazole in plasma over the time interval from 0 to the last quantifiable data point is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
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| COMPLETED | Completed Trial Medication |
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| NOT COMPLETED |
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| Washout (3 days) |
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| Period 2: (Test Period) (15 days) |
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Treated set (TS): The treated set includes all subjects who were treated with at least one dose of trial drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Repaglinide+Midazolam+Omeprazole (Reference)/ Zongertinib+Repaglinide+Midazolam+Omeprazole (Test) | Reference (Repaglinide + Midazolam + Omeprazole) In the reference treatment period (Period 1), participants received 0.5 mg repaglinide tablet (Day 1, after ≥10 h fast; Reference Treatment 1). On Day 2, they received 1 mg midazolam (0.5 mL oral solution) with 20 mg omeprazole tablet under the same fasting conditions (Reference Treatment 2). Test (Zongertinib + Repaglinide + Midazolam + Omeprazole) In the test treatment period (Period 2), participants received multiple once-daily doses of 120 mg zongertinib from Day 1 to Day 15. A single 0.5 mg repaglinide tablet was co-administered on Day 1 (Test Treatment 1) and Day 14 (Test Treatment 3), and a single dose of the probe drug cocktail containing 1 mg midazolam (0.5 mL oral solution) and 20 mg omeprazole tablet was co-administered on Day 2 (Test Treatment 2) and Day 15 (Test Treatment 4). |
| Units | Counts |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
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| Age, Continuous | Treated set (TS): The treated set includes all subjects who were treated with at least one dose of trial drug. | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Treated set (TS): The treated set includes all subjects who were treated with at least one dose of trial drug. | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Treated set (TS): The treated set includes all subjects who were treated with at least one dose of trial drug. | Count of Participants | Participants |
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| Race (NIH/OMB) | Treated set (TS): The treated set includes all subjects who were treated with at least one dose of trial drug. | Count of Participants | Participants |
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Area Under the Concentration-time Curve of Repaglinide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC₀-∞) | The area under the concentration-time curve of repaglinide in plasma over the time interval from 0 extrapolated to infinity ((AUC0-∞) is reported. Period 1 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 14): ≤15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 2.5, 3-, 4-,6-, and 24-hours post-dose. | Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) 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. Two subjects were discontinued by the investigator before Zongertinib administration on Day 2, leading to fewer subjects in Test Treatment 3 Arm. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours × picomoles per liter (h*pmol/L) | Samples were collected on Day 1 (Period 1), Day 1 (Period 2), and Day 14 (Period 2). See endpoint description for the full sampling schedule |
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| Primary | Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC₀-∞) | The area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity ((AUC0-∞) is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) 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. Two subjects were discontinued by the investigator before Zongertinib administration on Day 2, leading to fewer subjects in Test Treatment Arm 2 and 3. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours × picomoles per liter (h*pmol/L) | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
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| Primary | Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC₀-∞) | The area under the concentration-time curve of omeprazole in plasma over the time interval from 0 extrapolated to infinity ((AUC0-∞) is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) 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. Only participants with evaluable results were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour * nanogram per milliliter (h*ng/mL) | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
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| Primary | Maximum Measured Concentration of Repaglinide in Plasma (Cmax) | The maximum measured concentration of repaglinide in plasma is reported. Period 1 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 14): ≤15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 2.5, 3-, 4-,6-, and 24-hours post-dose. | Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) 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. Two subjects were discontinued by the investigator before Zongertinib administration on Day 2, leading to fewer subjects in Test Treatment 3 Arm. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picomoles per liter (pmol/L) | Samples were collected on Day 1 (Period 1), Day 1 (Period 2), and Day 14 (Period 2). See endpoint description for the full sampling schedule |
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| Primary | Maximum Measured Concentration of Midazolam in Plasma (Cmax) | The maximum measured concentration of midazolam in plasma is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) 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. Two subjects were discontinued by the investigator before Zongertinib administration on Day 2, leading to fewer subjects in Test Treatment Arm 2 and 3. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picomoles per liter (pmol/L) | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
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| Primary | Maximum Measured Concentration of Omeprazole in Plasma (Cmax) | The maximum measured concentration of omeprazole in plasma is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) 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. Only participants with evaluable results were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms per milliliter (ng/mL) | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
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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) | The area under the concentration-time curve of repaglinide in plasma over the time interval from 0 to the last quantifiable data poin is reported. Period 1 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 1): Up to 3 hours pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3-, 4-, 6-, and 24-hours post-dose. Period 2 (Day 14): ≤15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 2.5, 3-, 4-,6-, and 24-hours post-dose. | Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) 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. Two subjects were discontinued by the investigator before Zongertinib administration on Day 2, leading to fewer subjects in Test Treatment 3 Arm. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours × picomoles per liter (h*pmol/L) | Samples were collected on Day 1 (Period 1), Day 1 (Period 2), and Day 14 (Period 2). See endpoint description for the full sampling schedule |
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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) | The area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) 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. Two subjects were discontinued by the investigator before Zongertinib administration on Day 2, leading to fewer subjects in Test Treatment Arm 2 and 3. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours × picomoles per liter (h*pmol/L) | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
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| Secondary | Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | The area under the concentration-time curve of omeprazole in plasma over the time interval from 0 to the last quantifiable data point is reported. Period 1 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose. Period 2 (Day 2): 15 min pre-dose and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 12 h post-dose. Period 2 (Day 15): 15 min pre-dose, and at 15, 30, 45 min; 1, 1.5, 2, 4, 6, 8, 10, 11, 12 hours post-dose. | Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) 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. Only participants with evaluable results were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Samples were collected on Day 2 (Period 1), Day 2 (Period 2), and Day 15 (Period 2). See endpoint description for the full sampling schedule |
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AE collection timeframe: Repa (R1) & Zonger+Repa (T1, T3): up to 24h; Mida+Ome (R2) & Zonger+Mida+Ome (T2, T4): up to 48h; Zonger: up to 14d post-dose. All-cause mortality: Up to 50 days
Treated set (TS): The treated set includes all subjects 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) |
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| EG000 | Repaglinide (Reference Treatment 1) | Participants received a single 0.5 mg repaglinide tablet on Day 1 of Period 1, after an overnight fast of at least 10 hours. | 0 | 16 | 0 | 16 | 2 | 16 |
| EG001 | Midazolam + Omeprazole (Reference Treatment 2) | Participants received 1 mg midazolam (0.5 mL oral solution) coadministered with a 20 mg omeprazole tablet on Day 2 of Period 1, following an overnight fast of at least 10 hours. | 0 | 16 | 0 | 16 | 2 | 16 |
| EG002 | Zongertinib +Repaglinide (Test Treatment 1) | Participants received 120 mg zongertinib (two 60 mg tablets) and a single 0.5 mg repaglinide tablet on Day 1 of Period 2, after an overnight fast of at least 10 hours. | 0 | 16 | 0 | 16 | 4 | 16 |
| EG003 | Zongertinib +Midazolam +Omeprazole (Test Treatment 2) | Participants received 120 mg zongertinib (two 60 mg tablets) on Day 1. On Day 2, after one day of zongertinib pretreatment, participants were administered 1 mg, midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. | 0 | 14 | 0 | 14 | 4 | 14 |
| EG004 | Zongertinib | Participants received 120 mg zongertinib daily (as two 60 mg tablets) from Day 1 to Day 15 of Period 2. | 0 | 14 | 0 | 14 | 9 | 14 |
| EG005 | Zongertinib +Repaglinide (Test Treatment 3) | Participants received 0.5 mg repaglinide coadministered with zongertinib on Day 14 of Period 2, after 13 days of zongertinib pretreatment and an overnight fast. | 0 | 14 | 0 | 14 | 2 | 14 |
| EG006 | Zongertinib + Midazolam + Omeprazole (Test Treatment 4) | Participants received 1 mg midazolam and 20 mg omeprazole coadministered with zongertinib on Day 15 of Period 2, after 14 days of zongertinib pretreatment and an overnight fast. | 0 | 14 | 0 | 14 | 4 | 14 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrioventricular block second degree | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 27.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Cold sweat | Skin and subcutaneous tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Thrombophlebitis | Vascular disorders | MedDRA 27.0 | Systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 018002430127 | clintriage.rdg@boehringer-ingelheim.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 25, 2024 | Nov 4, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D008874 | Midazolam |
| D009853 | Omeprazole |
| C072379 | repaglinide |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D001562 | Benzimidazoles |
Not provided
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| The relative bioavailability of Repaglinide was assessed by comparing Repaglinide administered after multiple doses of zongertinib (Test Treatment 3) to Repaglinide administered alone (Reference Treatment 1). The ratio of geometric means (Test/Reference) with 90% two-sided confidence intervals (CIs) was calculated. The log-transformed difference (log[T]-log[R]) was estimated using least squares means from ANOVA and then back-transformed to the original scale. | Ratios of adjusted geometric means [%] | 130.10 | 2-Sided | 90 | 110.35 | 153.39 | Ratio calculated as test/reference*100. Intra-individual Geometric coefficient of variation [%] = 25.2 | Other |
| Midazolam + Omeprazole with a single dose of zongertinib (Test Treatment 2) |
In the test treatment period (Period 2), participants received 120 mg zongertinib (two 60 mg tablets) on Day 1. On Day 2, after one day of zongertinib pretreatment, participants were administered 1 mg, midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. |
| OG002 | Midazolam + Omeprazole after multiple doses of zongertinib (Test Treatment 4) | In the test treatment period (Period 2), participants received 120 mg Zongertinib daily (two 60 mg tablets) for 14 consecutive days. On Day 15, after 14 days of zongertinib treatment, participants received 1 mg midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. |
|
|
|
In the test treatment period (Period 2), participants received 120 mg zongertinib (two 60 mg tablets) on Day 1. On Day 2, after one day of zongertinib pretreatment, participants were administered 1 mg, midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. |
| OG002 | Midazolam + Omeprazole after multiple doses of zongertinib (Test Treatment 4) | In the test treatment period (Period 2), participants received 120 mg Zongertinib daily (two 60 mg tablets) for 14 consecutive days. On Day 15, after 14 days of zongertinib treatment, participants received 1 mg midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. |
|
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|
In the test treatment period (Period 2), Day 1, participants received a single 0.5 mg dose of repaglinide coadministered with a single 120 mg dose of zongertinib (two 60 mg tablets) following an overnight fast of at least 10 hours.
| OG002 | Repaglinide after multiple doses of zongertinib (Test Treatment 3) | In the test treatment period (period 2), participants received 120 mg zongertinib (two 60 mg tablets) daily for 13 consecutive days. On Day 14, after 13 days of zongertinib administration, a single dose of 0.5 mg repaglinide tablet was coadministered with 120 mg zongertinib following an overnight fast of at least 10 hours. |
|
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|
In the test treatment period (Period 2), participants received 120 mg zongertinib (two 60 mg tablets) on Day 1. On Day 2, after one day of zongertinib pretreatment, participants were administered 1 mg, midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours.
| OG002 | Midazolam + Omeprazole after multiple doses of zongertinib (Test Treatment 4) | In the test treatment period (Period 2), participants received 120 mg Zongertinib daily (two 60 mg tablets) for 14 consecutive days. On Day 15, after 14 days of zongertinib treatment, participants received 1 mg midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. |
|
|
|
| OG002 | Midazolam + Omeprazole after multiple doses of zongertinib (Test Treatment 4) | In the test treatment period (Period 2), participants received 120 mg Zongertinib daily (two 60 mg tablets) for 14 consecutive days. On Day 15, after 14 days of zongertinib treatment, participants received 1 mg midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. |
|
|
|
| Repaglinide with a single dose of zongertinib (Test Treatments 1) |
In the test treatment period (Period 2), Day 1, participants received a single 0.5 mg dose of repaglinide coadministered with a single 120 mg dose of zongertinib (two 60 mg tablets) following an overnight fast of at least 10 hours. |
| OG002 | Repaglinide after multiple doses of zongertinib (Test Treatment 3) | In the test treatment period (period 2), participants received 120 mg zongertinib (two 60 mg tablets) daily for 13 consecutive days. On Day 14, following 13 days of zongertinib administration, a single dose of 0.5 mg repaglinide tablet was coadministered with 120 mg zongertinib following an overnight fast of at least 10 hours. |
|
|
|
| Midazolam + Omeprazole after a single dose of zongertinib (Test Treatments 2) |
In the test treatment period (Period 2), participants received 120 mg zongertinib (two 60 mg tablets) on Day 1. On Day 2, after one day of zongertinib pretreatment, participants were administered 1 mg, midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. |
| OG002 | Midazolam + Omeprazole after multiple doses of zongertinib (Test Treatment 4) | In the test treatment period (Period 2), participants received 120 mg Zongertinib daily (two 60 mg tablets) for 14 consecutive days. On Day 15, after 14 days of zongertinib treatment, participants received 1 mg midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. |
|
|
|
In the test treatment period (Period 2), participants received 120 mg zongertinib (two 60 mg tablets) on Day 1. On Day 2, after one day of zongertinib pretreatment, participants were administered 1 mg, midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. |
| OG002 | Midazolam + Omeprazole after multiple doses of zongertinib (Test Treatment 4) | In the test treatment period (Period 2), participants received 120 mg Zongertinib daily (two 60 mg tablets) for 14 consecutive days. On Day 15, after 14 days of zongertinib treatment, participants received 1 mg midazolam, coadministered with 20 mg omeprazole, and zongertinib following an overnight fast of at least 10 hours. |
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