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.