Trial results for a Phase 1 study investigating the pharmacokinetic interactions of zongertinib with other medicines were posted on ClinicalTrials.gov on 2026-01-09. The study in healthy men showed that zongertinib increased the systemic exposure of dabigatran and rosuvastatin, with adjusted geometric mean ratios for AUC0-∞ of 133.98% and 230.3% respectively, while decreasing the exposure of metformin, with an AUC0-∞ ratio of 83.02%.
Background
The study, titled "A Study in Healthy Men to Test Whether Zongertinib Influences the Amount of 4 Other Medicines (Dabigatran, Rosuvastatin, Metformin, and Furosemide) in the Blood," focused on evaluating potential drug-drug interactions.
Trial design
The study (NCT06504862) was a Phase 1, completed trial that enrolled 32 healthy male participants. The trial investigated the effect of zongertinib on the pharmacokinetics of dabigatran-etexilate, rosuvastatin, metformin hydrochloride, and furosemide. Part 1 assessed the effect of a single dose of zongertinib on the pharmacokinetics of a single dose of dabigatran-etexilate. Part 2 assessed the effect of zongertinib at steady-state on the pharmacokinetics of a single dose of rosuvastatin, metformin, and furosemide (administered as a cocktail).
Key results
The trial evaluated the pharmacokinetic parameters of the co-administered drugs:
- For dabigatran, co-administration with zongertinib resulted in an adjusted geometric mean ratio for AUC0-∞ of 133.98% (90.0% CI: 105.52 to 170.11) compared to dabigatran alone. The Cmax ratio was 124.19% (90.0% CI: 96.13 to 160.43).
- For rosuvastatin, co-administration with zongertinib resulted in an adjusted geometric mean ratio for AUC0-∞ of 230.3% (90.0% CI: 195.68 to 271.04) compared to the drug cocktail alone. The Cmax ratio was 301.68% (90.0% CI: 247.19 to 368.19).
- For metformin, co-administration with zongertinib resulted in an adjusted geometric mean ratio for AUC0-∞ of 83.02% (90.0% CI: 76.48 to 90.12) compared to the drug cocktail alone. The Cmax ratio was 75.57% (90.0% CI: 68.03 to 83.95).
Specific geometric least squares mean values were:
- Dabigatran AUC0-∞: 725.25 h*ng/mL (R) vs. 971.67 h*ng/mL (T).
- Dabigatran Cmax: 89.01 ng/mL (R) vs. 110.53 ng/mL (T).
- Rosuvastatin AUC0-∞: 102.98 h*nmol/L (R) vs. 237.15 h*nmol/L (T).
- Rosuvastatin Cmax: 8.87 nmol/L (R) vs. 26.75 nmol/L (T).
- Metformin AUC0-∞: 1355.69 h*nmol/L (R) vs. 1125.52 h*nmol/L (T).
- Metformin Cmax: 230.25 nmol/L (R) vs. 174.00 nmol/L (T).
What this means
The results indicate that zongertinib has significant pharmacokinetic interactions with dabigatran, rosuvastatin, and metformin. The increased exposure to dabigatran and rosuvastatin suggests a potential for increased pharmacological effects or adverse events if these drugs are co-administered without dose adjustments. Conversely, the decreased exposure to metformin could lead to reduced efficacy. These findings highlight the importance of considering potential drug-drug interactions when prescribing zongertinib with these medications.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT06504862, titled "A Study in Healthy Men to Test Whether Zongertinib Influences the Amount of 4 Other Medicines (Dabigatran, Rosuvastatin, Metformin, and Furosemide) in the Blood," were posted on 2026-01-09 on clinicaltrials.gov.