Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Zibotentan · 5 trials · 5 indications
The effect of zibotentan 1.5/dapagliflozin 10 mg versus dapagliflozin 10 mg on UACR was assessed.
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants.
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants.
To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
To assess the PK of a single oral dose of zibotentan in participants with moderate hepatic impairment and moderate renal impairment compared to a group of healthy matched controls
To assess the PK of a single oral dose of zibotentan in participants with moderate hepatic impairment and moderate renal impairment compared to a group of healthy matched controls
To assess the PK of a single oral dose of zibotentan in participants with moderate hepatic impairment and moderate renal impairment compared to a group of healthy matched controls
Plasma sample will be collected to understand the PK profiling of zibotentan metabolites and to meet the regulatory requirements.
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
| Arm | Type | Description |
|---|---|---|
| Zibotentan Dose A + Dapagliflozin | EXPERIMENTAL | Participants will receive once daily oral dose A of zibotentan and 10 mg dapagliflozin for 12 weeks. |
| Zibotentan Dose B + Dapagliflozin | EXPERIMENTAL | Participants will receive once daily oral dose B of zibotentan and 10 mg dapagliflozin for 12 weeks. |
| Placebo + Dapagliflozin | EXPERIMENTAL | Participants will receive once daily oral dose of dapagliflozin 10 mg and placebo for 12 weeks. |
| Treatment sequence ABCD: Zibotentan | EXPERIMENTAL | Participants will receive single dose of Zibotentan in 4 occassions with first Treatment A, followed by Treatment B, Treatment C and then Treatment D with each dose separated by 3 washout periods. |
| Treatment sequence BDAC: Zibotentan | EXPERIMENTAL | Participants will receive single dose of Zibotentan in 4 occassions with first Treatment B, followed by Treatment D, Treatment A and then Treatment C with each dose separated by 3 washout periods |
| Treatment sequence CADB: Zibotentan | EXPERIMENTAL | Participants will receive single dose of Zibotentan in 4 occassions with first Treatment C, followed by Treatment A, Treatment D and then Treatment B with each dose separated by 3 washout periods. |
| Treatment sequence DCBA: Zibotentan | EXPERIMENTAL | Participants will receive single dose of Zibotentan in 4 occassions with first Treatment D, followed by Treatment C, Treatment B and then Treatment A with each dose separated by 3 washout periods. |
| Zibotentan and EE/LNG | EXPERIMENTAL | Participants will receive two tablets of combined oral EE/LNG on Day 1 with PK samples obtained from pre-dose on Day 1 until post-dose on Day 6. Participants will receive two capsules of zibotentan orally QD from Day 6 to Day 14. From Day 15 until Day 19 participants will continue to receive two capsules of zibotentan QD administered orally. On Day 15, participants will receive two tablets of combined oral EE and LNG with PK samples obtained pre-dose on Day 15 until post-dose (Day 20). |
| Cohort 1: Participants with moderate hepatic impairment and moderate renal impairment | EXPERIMENTAL | Participants will receive a single oral dose of zibotentan under fasted conditions. |
| Cohort 2: Healthy participants | EXPERIMENTAL | Participants will receive a single oral dose of zibotentan under fasted conditions. |
| Part 1 | EXPERIMENTAL | Participants will be administered with zibotentan once daily for 5 days. |
| Part 2: Treatment Sequence ABC | EXPERIMENTAL | Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment A; Treatment B; Treatment C) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods. |
| Part 2: Treatment Sequence BCA | EXPERIMENTAL | Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment B; Treatment C; Treatment A) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods. |
| Part 2: Treatment Sequence CAB | EXPERIMENTAL | Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment C; Treatment A; Treatment B) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods. |
| Name | Type | Description |
|---|---|---|
| Zibotentan | DRUG | Participants will receive zibotentan as per the arms they are randomized. |
| Dapagliflozin | DRUG | Participants will receive 10 mg dapagliflozin as per the arms they are randomized. |
| Placebo | DRUG | Participants will receive placebo as per the arms they are randomized to. |
| EE/LNG | DRUG | Participants will receive two tablets of EE and LNG once on Day 1 and Day 15 as a combined oral dose. |
| Zibotentan (Treatment A) | DRUG | Zibotentan capsule will be administered orally as multiple doses in Part 1 and as single dose in Part 2. |
| Dapagliflozin (Treatment A) | DRUG | Dapagliflozin tablet will be administered orally as single dose in Part 2. |
| Zibotentan/Dapagliflozin - Formulation 1 (Treatment B) | DRUG | Zibotentan/Dapagliflozin tablet will be administered orally as single dose in Part 2. |
| Zibotentan/Dapagliflozin - Formulation 2 (Treatment C) | DRUG | Zibotentan/Dapagliflozin tablet will be administered orally as single dose in Part 2. |
Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: * Diagnosis of Chronic kidney disease (CKD), defined as: (a) eGFR chronic kidney disease epidemiology collaboration (CKD-EPI) ≥ 20 mL/min/1.73 m\^2, and (b) UACR ≥ 150 and ≤ 50...
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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.