Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as AZD9977
Balcinrenone · 8 trials · 8 indications
Time from randomization to first occurrence of any of the components of the composite: * CV death * Death from kidney failure * Onset of kidney failure * Initiation of maintenance dialysis or * Kidney transplantation * Sustained ≥ 50% decline from baseline in eGFR * HF with or without hospitalisation
The effect of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone on UACR assessed. Urine samples were collected for the analysis of UACR. UACR (milligrams per gram \[mg/g\]) was calculated as 10 x urine albumin (mg per deciliter \[mg/dL\])/urine creatinine (g/dL). Change from baseline in UACR at the end of 12 weeks of study treatment was calculated as the average of the UACR values at Week 12 and was analyzed by a mixed-effects model for repeated measures (MMRM). Due to early removal of arms (AZD9977 150 mg monotherapy and Placebo), the study objectives were revised and the MMRM analysis included the 4 remaining arms (AZD9977 15 mg + Dapagliflozin, AZD9977 50 mg + Dapagliflozin, AZD9977 150 mg + Dapagliflozin, and Dapagliflozin 10 mg). Since 2 arms were removed from the study resulting in fewer participants only descriptive statistics are shown for those two arms without formal comparison.
To evaluate the effect of HD on the PK of balcinrenone/dapagliflozin
To evaluate the effect of HD on the PK of balcinrenone/dapagliflozin
To evaluate the effect of HD on the PK of balcinrenone/dapagliflozin
To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD
To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD
To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD
To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD
To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD
To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD
To evaluate the PK of balcinrenone/dapagliflozin in dialysate in participants with kidney failure on HD
To evaluate the PK of balcinrenone/dapagliflozin in dialysate in participants with kidney failure on HD
To evaluate the PK of balcinrenone/dapagliflozin in dialysate in participants with kidney failure on HD
To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD
To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD
To compare the PK of a single oral dose of balcinrenone in participants with mild and moderate hepatic impairment to those with normal hepatic function
To compare the PK of a single oral dose of balcinrenone in participants with mild and moderate hepatic impairment to those with normal hepatic function
To compare the PK of a single oral dose of balcinrenone in participants with mild and moderate hepatic impairment to those with normal hepatic function
Absolute bioavailability based on AUC0-inf of oral formulation compared to IV adjusted for dose
Assessment of the total radioactivity by measuring the cumulative amount of AZD9977 excreted (CumAe)
Assessment of the rates and routes of elimination by measuring the cumulative amount excreted and expressed as a percentage of the administered dose (CumFe)
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To assess the PK of AZD9977 following administration of AZD9977
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Serious AEs will be recorded from the time of screening.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Blood pressure includes both systolic and diastolic BP.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. The complete physical examinations will include an assessment of the general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Electrolyte Measurements includes Bicarbonate, Calcium, Chloride, Potassium, Sodium
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants.
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Microscopy should be done (if positive for protein or blood): red blood cells (RBC), white blood cells (WBC), Casts (Cellular, Granular, Hyaline)
To investigate the safety and tolerability of AZD9977 following oral administration of single and multiple ascending doses at steady state in healthy Japanese participants. Urinary Electrolytes: Calcium, Potassium, Chloride, Sodium, Creatinine and Uric acid.
| Arm | Type | Description |
|---|---|---|
| Balcinrenone/dapagliflozin | EXPERIMENTAL | Patient receives once daily 1 capsule balcinrenone 15 mg and dapagliflozin 10 mg and 1 placebo tablet matching dapagliflozin. |
| Dapagliflozin | ACTIVE_COMPARATOR | Patient receives once daily 1 placebo capsule matching balcinrenone and dapagliflozin and 1 tablet dapagliflozin 10 mg. |
| AZD9977 Dose A + dapagliflozin 10 mg | EXPERIMENTAL | Participants will receive once daily oral dose A of AZD9977 and 10 mg dapagliflozin for 12 weeks. |
| AZD9977 Dose B + dapagliflozin 10 mg | EXPERIMENTAL | Participants will receive once daily oral dose B of AZD9977 and 10 mg dapagliflozin for 12 weeks. |
| AZD9977 Dose C + dapagliflozin 10 mg | EXPERIMENTAL | Participants will receive once daily oral dose C of AZD9977 and 10 mg dapagliflozin for 12 weeks. |
| Dapagliflozin 10 mg | EXPERIMENTAL | Participants will receive once daily oral dose of dapagliflozin 10 mg alone for 12 weeks. |
| Sequence AB | OTHER | Participants will receive Treatment A (balcinrenone/dapagliflozin capsule administered 1,5 hours before the start of a 4-hour hemodialysis session) on Day 1. After a wash-out period of ≥ 7 days, participants will receive Treatment B (balcinrenone/dapagliflozin capsule administered 1 hour after the completion of a 4-hour hemodialysis session) |
| Sequence BA | OTHER | Participants will receive Treatment B (balcinrenone/dapagliflozin capsule administered 1 hour after the completionof a 4-hour hemodialysis session) on Day 1. After a wash-out period of ≥ 7 days, participants will receive Treatment A (balcinrenone/dapagliflozin capsule administered 1.5 hours before the start of a 4-hour hemodialysis session) |
| Group 1 | EXPERIMENTAL | Subjects with Mild Impairment will receive a single oral dose of balcinrenone under fasted conditions. |
| Group 2 | EXPERIMENTAL | Subjects with Moderate Impairment will receive a single oral dose of balcinrenone under fasted conditions. |
| Group 3 | EXPERIMENTAL | Healthy participants will receive a single oral dose of balcinrenone under fasted conditions. |
| AZD9977 | EXPERIMENTAL | In Period 1, one 100 mg dose of AZD9977 capsule 50 mg (as 2 x 50 mg capsules) and one 100 µg dose of \[14C\]AZD9977 Solution for Infusion, 20 µg/mL (NMT 37.0 kBq/5 mL). In Period 2, one 100 mg dose of \[14C\]AZD9977 Oral Suspension, 100 mg (NMT 9.9 MBq). |
| Treatment - AZD9977 | EXPERIMENTAL | There are 4 cohorts in this arm based on renal function (mild, moderate, severe, and normal). Each cohort will have 8 participants. |
| Single AZD9977 | EXPERIMENTAL | During this treatment period, healthy participants will be administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period. |
| Itraconazole + AZD9977 | EXPERIMENTAL | During this treatment period, healthy participants will be administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus will be administrated with AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole will be taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977. |
| Placebo | PLACEBO_COMPARATOR | Each participant will receive placebo at the selected dose level on Day 1 and from Day 3 to 9, with single dose on Day 1 and Day 9 and twice a day (BID) dosing on Day 3 to Day 8. No dose will be given on Day 2. |
| Name | Type | Description |
|---|---|---|
| Balcinrenone/dapagliflozin | DRUG | balcinrenone/dapagliflozin 15 mg/10 mg |
| Dapagliflozin | DRUG | dapagliflozin 10 mg |
| Placebo matching Dapagliflozin | DRUG | matching placebo for dapagliflozin 10 mg |
| Placebo matching balcinrenone/dapagliflozin | DRUG | matching placebo for balcinrenone/dapagliflozin |
| AZD9977 | DRUG | Participants will receive AZD9977 as per the arms they are randomized. |
| Balcinrenone | DRUG | 50 mg, Immediate release capsule to be taken orally. |
| AZD9977 capsule 50 mg | DRUG | 100 mg dose of AZD9977 capsule 50 mg (as 2 x 50 mg capusles) |
| [14C]AZD9977 Solution for Infusion, 20 µg/mL (NMT 37.0 kBq/5 mL) | DRUG | One 100 µg dose of \[14C\]AZD9977 Solution for Infusion, 20 µg/mL (NMT 37.0 kBq/5 mL) |
| [14C]AZD9977 Oral Suspension, 100 mg (NMT 9.9 MBq) | DRUG | One 100 mg dose of \[14C\]AZD9977 Oral Suspension, 100 mg (NMT 9.9 MBq) |
| Itraconazole | DRUG | Participants will receive Itraconazole daily (Dose 2) capsule orally once daily from Day 4 to Day 8 plus will be administered AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole has to be taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977. |
| Placebo | DRUG | Randomized participants will receive oral dose of matching placebo. |
Inclusion Criteria: * Age ≥ 18 years * Diagnosis of CKD and at least one of the following: 1. eGFR ≥ 15 to \< 45 mL/min/1.73 m2 AND: UACR ≥ 30 mg/g (central laboratory) or UACR ≥ 100 mg/g (local laboratory ) or UPCR ≥ 200 mg/g (local laboratory). 2. eGFR ≥ 15 to \< 30 mL/min/1.73 m2 and UACR \...
Balcinrenone is an investigational small molecule being studied for chronic kidney disease and related kidney conditions. It is being evaluated in patients with chronic renal insufficiency and kidney failure, including a Phase 3 study in CKD stage 3b and 4. It is also being studied in hepatic impairment. It is not approved for any indication.
Balcinrenone targets NR3C2, also known as the mineralocorticoid receptor. It is a modulator of this receptor. By acting on NR3C2, balcinrenone is designed to affect mineralocorticoid receptor signaling, which is relevant to kidney and cardiovascular physiology. The drug is a small molecule.
Balcinrenone is being developed by AstraZeneca PLC, which trades on the Nasdaq under the ticker AZN. AstraZeneca is the sponsor of the clinical trials evaluating balcinrenone, including the Phase 3 BalanceD-CKD study and Phase 1 pharmacokinetic studies.
Balcinrenone is in clinical development, with a Phase 3 trial currently recruiting and Phase 1 trials completed or ongoing. It is investigational and has not been approved by the FDA or any regulatory authority. The Phase 3 study is evaluating balcinrenone/dapagliflozin in CKD stage 3b and 4.
Balcinrenone is being studied in three registered trials. NCT07624305 is a Phase 3 study of balcinrenone/dapagliflozin in CKD stage 3b and 4, recruiting 2,800 patients. NCT07754331 is a Phase 1 study of hemodialysis effects on balcinrenone/dapagliflozin pharmacokinetics. NCT06388616 is a completed Phase 1 hepatic impairment study.