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Also known as baxdrostat 2mg, Baxdrostat and dapagliflozin
Baxdrostat · 13 trials · 6 indications
To assess the effect of baxdrostat 2mg versus placebo on ambulatory 24-hour average SBP at 12 weeks
Change in LVMi (g/m\^2), measured by cardiac magnetic resonance imaging (cMRI) from baseline to 12 months of treatment with baxdrostat compared to placebo.
To assess the effect of baxdrostat versus placebo on seated Systolic Blood Pressure (SBP) at Week 8
To assess the effect of baxdrostat vs placebo on achieving normalization of renin at week 8
To assess the effect of 2 mg baxdrostat versus placebo on seated SBP at Week 12
To assess the effect of 2 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed.
To assess the effect of 1 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed.
The primary endpoint is individual participant's cortisol levels at each timepoint. Number of participants with normal stimulated serum total cortisol level at baseline are presented here. Characterisation of the serum total cortisol levels before and after ACTH stimulation test. An ACTH stimulation test using 250 μg ACTH was performed at baseline and Week 8 (End of Treatment), with serum cortisol level measured before and after ACTH stimulation test. Normal cortisol levels are defined as at least 18 μg/dL when measured 60 minutes (±10 minutes) after stimulation. If the Week 8 results show abnormal levels, a repeat test is conducted. In this repeat test, cortisol is considered abnormal only if both of the following conditions are met: the level is less than 14.8 μg/dL at 30 minutes (± 5 minutes) and less than 18 μg/dL at 60 minutes (±10 minutes).
The effect of itraconazole on the PK (AUCinf) of baxdrostat will be assessed.
The effect of itraconazole on the PK (Cmax) of baxdrostat will be assessed.
The effect of single doses of baxdrostat on QTcF compared to placebo using a concentration-QTcF analysis will be assessed.
Safety and tolerability will be assessed by comparison of number of treatment emergent adverse events between groups.
AUC \[0 to 24 hours, 0 to last quantifiable concentration, and 0 to infinity of baxdrostat\] will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.
Cmax will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.
Plasma aldosterone levels will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.
Tmax will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.
Terminal elimination half-life will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.
Measurement of total radioactivity recovery in urine and feces to determine the routes, rates of elimination, and mass balance of total radioactivity from \[14C\] baxdrostat.
Area under the curve (AUC)0-∞ and AUC0-last will be determined for baxdrostat and CIN-107M in plasma.
Determining cumulative amount of baxdrostat and CIN-107M excreted in urine, clearance of baxdrostat and CIN-107M, and fraction of dose excreted renally (baxdrostat only).
Cmax will be determined based on measurement of baxdrostat and CIN-107M in plasma.
Tmax will be determined based on measurement of baxdrostat and CIN-107M in plasma.
t1/2 for baxdrostat and CIN-107M in plasma will be determined based on measurement of baxdrostat and CIN-107M in plasma.
The safety and tolerability of baxdrostat was assessed throughout the study based on incidence of treatment emergent adverse events (AEs), following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.
Measurement of plasma concentrations of baxdrostat and its major metabolite CIN-107-M. AUC \[0 to 24 hours, 0 to last quantifiable concentration, and 0 to infinity of baxdrostat\] will be determined for baxdrostat and the CIN-107M metabolite.
Cmax will be determined for baxdrostat and the CIN-107M metabolite
Tmax will be determined for baxdrostat and the CIN-107M metabolite
Terminal elimination half-life will be determined for baxdrostat and the CIN-107M metabolite
The safety and tolerability of CIN-107 will be assessed throughout the study based on quantitation of adverse events that occur following oral doses of CIN-107 tablet and oral solution.
Cmax will be determined for CIN-107 and any other measured metabolites for participants given each formulation of baxdrostat; relative bioavailability will be evaluated by comparing these parameters between patients given the solution versus the tablet.
Cmax will be determined for CIN-107 and any other measured metabolites for participants given baxdrostat under fed versus fasted conditions; food effect will be evaluated by comparing Cmax between participants under each condition.
Area under the curve (AUC)0-∞ and AUC0-last will be determined for baxdrostat and any other measured metabolites for participants given each formulation of baxdrostat. Then relative bioavailability will be evaluated by comparing these AUC parameters between patients given the solution versus the tablet.
Tmax will be determined for CIN-107 and any other measured metabolites for participants given baxdrostat under fed versus fasted conditions, and then food effect will be evaluated by comparing Tmax between participants under each condition.
Area under the curve (AUC)0-∞ and AUC0-last will be determined for CIN-107 and any other measured metabolites for participants given baxdrostat under fed versus fasted conditions, and then food effect will be evaluated by comparing AUC between participants under each condition.
Tmax will be determined for CIN-107 and any other measured metabolites for participants given each formulation of baxdrostat.
| Arm | Type | Description |
|---|---|---|
| baxdrostat 2 mg | EXPERIMENTAL | 2 mg baxdrostat administered orally, once daily (QD) |
| Placebo 2mg | PLACEBO_COMPARATOR | 2 mg placebo administered orally, once daily (QD) |
| Baxdrostat | ACTIVE_COMPARATOR | Active treatment group |
| Placebo | PLACEBO_COMPARATOR | Control treatment group |
| 2 mg baxdrostat | EXPERIMENTAL | 2 mg baxdrostat administered orally, once daily (QD) |
| 1 mg baxdrostat | EXPERIMENTAL | 1 mg baxdrostat administered orally, once daily (QD). |
| Arm 1: Baxdrostat 2 mg | EXPERIMENTAL | Participants will receive baxdrostat 2 mg tablet orally once daily. |
| Arm 2: Placebo | PLACEBO_COMPARATOR | Participants will receive placebo tablet orally once daily. |
| Baxdrostat and Itraconazole | EXPERIMENTAL | Participants will receive single dose of baxdrostat tablet orally on Day 1 in Period 1, followed by itraconazole capsule orally twice a day on Day 6 and once daily on Days 7 to 8 in Period 2, and then single dose of baxdrostat tablet orally on Day 9 with itraconazole capsule orally once daily on Days 9 to 16 in Period 3. |
| Treatment Sequence ABCD | EXPERIMENTAL | Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (ABCD) in a crossover design with a washout period of at least 7 days between each study dose administration. |
| Treatment Sequence BDAC | EXPERIMENTAL | Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (BDAC) in a crossover design with a washout period of at least 7 days between each study dose administration. |
| Treatment Sequence CADB | EXPERIMENTAL | Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (CADB) in a crossover design with a washout period of at least 7 days between each study dose administration. |
| Treatment Sequence DCBA | EXPERIMENTAL | Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (DCBA) in a crossover design with a washout period of at least 7 days between each study dose administration. |
| Cohort 1 | EXPERIMENTAL | Oral tablet dose of baxdrostat 1 mg or placebo, administered as a single dose (Day 1) and multiple doses (once daily \[QD\] for 5 days, Days 6 - 10) to Japanese subjects |
| Cohort 2 | EXPERIMENTAL | Oral tablet dose of baxdrostat 3 mg or placebo, administered as a single dose (Day 1) and multiple doses (QD for 5 days, Days 6 - 10) to Japanese subjects |
| Cohort 3 | EXPERIMENTAL | Oral tablet dose of baxdrostat 3 mg or placebo, administered as a single dose (Day 1) and multiple doses (QD for 5 days, Days 6 - 10) to Caucasian subjects |
| Cohort 4 | EXPERIMENTAL | Oral tablet dose of baxdrostat 10 mg or placebo, administered as a single dose (Day 1) and multiple doses (QD for 5 days, Days 6 - 10) to Japanese subjects |
| 10 mg [14C]-bexdrostat | EXPERIMENTAL | single oral dose of 10 mg baxdrostat containing 100 μCi of \[14C\] baxdrostat |
| Normal hepatic function group | EXPERIMENTAL | Subjects with normal hepatic function |
| Moderate hepatic impairment group | EXPERIMENTAL | Subjects with a Child-Pugh score of 7 to 9 (Category B) at screening |
| Baxdrostat oral solution | EXPERIMENTAL | 5 mg CIN-107 oral solution in a fasted state |
| Baxdrostat tablet (fasted state) | EXPERIMENTAL | 5 mg CIN-107 tablet(s) in a fasted state |
| Baxdrostat tablet (fed state) | EXPERIMENTAL | 5 mg CIN-107 tablet(s) in a fed state (standard high fat meal) |
| Name | Type | Description |
|---|---|---|
| baxdrostat 2mg | DRUG | baxdrostat 2mg tablet administered orally, once daily (QD). |
| Placebo 2mg | DRUG | Placebo 2mg tablet administered orally, once daily (QD). |
| Baxdrostat | DRUG | Participants will take 2mg baxdrostat (Baxfendy) once daily (orally), in addition to standard-of-care. |
| Placebo | DRUG | Participants will take placebo once daily (orally), in addition to standard-of-care. |
| Itraconazole | DRUG | Itraconazole capsule will be administered orally. |
| Moxifloxacin | DRUG | Participants will receive a single dose moxifloxacin |
| baxdrostat (formerly CIN-107) oral solution | DRUG | 5 mg single dose of baxdrostat given as either a solution or tablet in either the fed or fasted state, depending on the arm of the study |
Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age 1. Participant must be ≥18 years old, at the time of signing the informed consent. Type of Participant and Disease Characteristics 1. Mean seated SBP on AOBPM ≥140 mmHg and ...
Baxdrostat is an investigational small molecule being studied for uncontrolled hypertension and resistant hypertension, as well as for cardiac remodeling, heart failure, chronic kidney disease with hypertension, and primary hyperaldosteronism. It is being evaluated in Phase 3 clinical trials for hypertension indications.
Baxdrostat is a small molecule that targets aldosterone synthase, the enzyme responsible for aldosterone production. By inhibiting this enzyme, it aims to reduce aldosterone levels, which may help lower blood pressure in patients with hypertension, including those with resistant hypertension.
Baxdrostat is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker symbol AZN. AstraZeneca is conducting clinical trials to evaluate the drug's efficacy and safety in patients with hypertension and related conditions.
Baxdrostat is in Phase 3 clinical development for uncontrolled hypertension and resistant hypertension. It is also being studied in earlier phase trials for related conditions. Baxdrostat is investigational and has not been approved by regulatory authorities for any use.
Baxdrostat has been studied in several clinical trials, including NCT06034743 and NCT06344104, both Phase 3 trials in patients with uncontrolled hypertension on two or more medications, including those with resistant hypertension. A Phase 2 trial, NCT06336356, evaluated cortisol reserve following treatment. A Phase 3b trial, NCT07686120, is planned in Chinese participants with uncontrolled hypertension.
Baxdrostat is also known as Baxdrostat/dapagliflozin, baxdrostat 2mg, and Baxdrostat and dapagliflozin. These names refer to the same drug, baxdrostat, which is being studied alone or in combination with dapagliflozin for hypertension and related conditions.