Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Zibotentan/Dapagliflozin · 3 trials · 2 indications
To determine whether zibotentan and dapagliflozin in fixed dose combination is superior to dapagliflozin alone to slow decline in kidney function
To estimate the efficacy of zibotentan and dapagliflozin in FDC versus dapagliflozin alone in reducing albuminuria
To investigate the effect of a high fat, high calorie meal, in comparison to fasting conditions, on the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.
To investigate the effect of a high fat, high calorie meal, in comparison to fasting conditions, on the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.
To investigate the effect of a high fat, high calorie meal, in comparison to fasting conditions, on the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.
| Arm | Type | Description |
|---|---|---|
| Zibotentan/Dapagliflozin dose A or Zibotentan/Dapagliflozin dose B | EXPERIMENTAL | Drug dose (dose A or B) are determined based on eGFR values. Participants will receive daily oral dose of zibotentan/dapagliflozin in fixed dose combination. |
| Dapagliflozin alone | ACTIVE_COMPARATOR | Participants will receive daily oral dose of dapagliflozin. |
| Treatment AB | EXPERIMENTAL | Participants will receive single dose of Zibotentan/Dapagliflozin FDC after an overnight fast of at least 10 hours (Treatment A). After a washout period, participants will receive another single dose of Zibotentan/Dapagliflozin FDC 30 minutes after having a high-fat, high-calorie standardized meal (Treatment B). |
| Treatment BA | EXPERIMENTAL | Participants will receive single dose of Zibotentan/Dapagliflozin FDC 30 minutes after having a high-fat high-calorie standardized meal (Treatment B). After a washout period, participants will receive another single dose of Zibotentan/Dapagliflozin FDC after an overnight fast of at least 10 hours (Treatment A). |
| Name | Type | Description |
|---|---|---|
| Zibotentan/Dapagliflozin | DRUG | Participants will receive zibotentan/dapagliflozin in fixed-dose combination as per the arms they are randomized to |
| Dapagliflozin | DRUG | Participants will receive dapagliflozin as per the arms they are randomized to |
| Zibotentan/Dapagliflozin FDC | DRUG | Zibotentan/Dapagliflozin FDC will be administered as an oral tablet. |
Inclusion Criteria: 1. Participant must be ≥ 18 years of age and of legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent. 2. Diagnosis of CKD, defined as eGFR ≥ 20 and \< 90 mL/min/1.73 m2 and UACR \> 700 mg/g (\> 79 mg/mmol) or UP...
Zibotentan is an investigational small molecule being studied for chronic kidney disease, including chronic kidney disease with high proteinuria, as well as hepatic impairment and liver cirrhosis. It is also being evaluated in healthy participants for pharmacokinetic studies. Zibotentan is not approved and remains in clinical development.
Zibotentan is an endothelin receptor antagonist. It is being studied in combination with dapagliflozin for the treatment of chronic kidney disease. The combination is being evaluated in the ZENITH-CKD trial.
Zibotentan is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker AZN. AstraZeneca is conducting clinical trials to evaluate Zibotentan for chronic kidney disease and related conditions.
Zibotentan is in Phase 2 clinical development. The most advanced trial, the ZENITH-CKD study, is a Phase 2 trial that has been completed. Zibotentan is investigational and has not been approved by regulatory authorities.
Zibotentan has been studied in several clinical trials, including NCT04724837, a Phase 2 trial in chronic kidney disease with 542 participants, and NCT04991571, a Phase 1 trial in healthy participants. Additional Phase 1 trials include NCT05112419 in hepatic and renal impairment and NCT05505162 in healthy female participants.
Zibotentan is also known as Zibotentan/Dapagliflozin when referring to the combination therapy being studied. In clinical trials, Zibotentan is often evaluated in combination with dapagliflozin for the treatment of chronic kidney disease.