Chronic Kidney Disease
Conditions
Keywords
Albuminuria, Arterial hypertension, Hypertension, Proteinuria, Diabetic nephropathy, Chronic Kidney Disease, Aldosterone Synthase Inhibitor
Brief summary
This is a randomized, double-blind (DB), placebo controlled, crossover study with a two-period, two-sequence (2x2) design evaluating the efficacy and safety of 25 mg QD lorundrostat (an aldosterone synthase inhibitor \[ASI\]) in addition to a SGLT2i for the treatment of hypertension in subjects with CKD and albuminuria while receiving stable treatment with an Angiotensin-converting enzyme inhibitor (ACEi) or an Angiotensin receptor blocker (ARB). Subjects will be at least 18 years old with hypertension, and mild to severe CKD with albuminuria at the Screening Visit.
Detailed description
The study consists of up to a 2-week Screening period, a 2-week run-in period where subjects will either begin study provided dapagliflozin 10 mg or continue on their regularly prescribed SGLT2i, and two DB 4-week treatment periods separated by a 4-week washout period. Subjects will be randomized (1:1) to two treatment sequences: lorundrostat-placebo (LP) and placebo-lorundrostat (PL).
Interventions
DRUGLorundrostat 25mg+SGLT2i QD, Washout, Placebo+SGLT2i QD
Period 1 - Lorundrostat 25mg QD + SGLT2i QD 4 weeks; Washout - Placebo QD + SGLT2i QD 4 weeks; Period 2 - Placebo QD + SGLT2i QD 4 weeks
DRUGPlacebo QD + SGLT2i QD, Washout, Lorundrostat 25mg+SGLT2i QD
Period 1 - Placebo QD + SGLT2i QD 4 weeks; Washout - Placebo QD + SGLT2i QD 4 weeks; Period 2 - Lorundrostat 25mg + SGLT2i QD 4 weeks
Sponsors
Mineralys Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: 1. At Screening, UACR of 200-5000 mg/g, inclusive, in first morning urine void 2. At Screening, eGFRs of ≥30 mL/min/1.73 m2 3. At Screening, AOBP SBP of 135-180 mmHg, inclusive 4. On a stable treatment with an ACEi or ARB for at least 2 months prior to Screening 5. At Screening, body mass index (BMI) of \>18 kg/m2 Major
Exclusion criteria
1. Subjects with known hypersensitivity to lorundrostat or any of its respective excipients 2. Subjects with known hypersensitivity to dapagliflozin or any of its respective excipients (subjects beginning dapagliflozin only) 3. At Screening, serum potassium \>5.0 mmol/L 4. History of clinically significant hyponatremia within 1 year prior to Screening 5. Use of epithelial sodium channel (ENaC) inhibitors or Mineralocorticoid receptor antagonist (MRAs), including, but not limited to amiloride, triamterene, spironolactone, eplerenone, finerenone, from 4 weeks prior to the Screening Visit and during study participation. With the exception of MRAs in primary aldosteronism 6. Medical history of kidney disease related to autoimmune diseases (lupus, anti-neutrophil cytoplasmic antibody \[ANCA\] vasculitis), multiple myeloma or other known paraproteins, infiltrative diseases of the kidney, obstructive nephropathy, cystic kidney diseases, and renal transplantation 7. Medical history of advanced liver disease, including cirrhosis 8. Medical history of active autoimmune disease or recent (within 30 days) or anticipated need for immunosuppressive therapy 9. Diabetes mellitus with a glycosylated hemoglobin (HbA1c) \>10% (\>86 mmol/mol) at Screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Placebo-adjusted Change From Baseline in Automated Office Blood Pressure (AOBP) Systolic Blood Pressure (SBP) at Week 4 | Baseline to Week 4 |
Countries
United States
Participant flow
Pre-assignment details
The study consisted of a Screening period of up to 2-weeks, a 2-week run-in period where subjects either began study provided dapagliflozin 10 mg or continued on their regularly prescribed SGLT2i, and two double-blind 4-week treatment periods separated by a 4-week washout period. Subjects were randomized (1:1) to two treatment sequences: lorundrostat-placebo (LP) and placebo-lorundrostat (PL).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 33 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age, Continuous | 64.8 Years STANDARD_DEVIATION 11.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 39 Participants |
| Region of Enrollment United States | 30 Participants |
| Seated Automated Office Blood Pressure (AOBP), Systolic | 147.008 mmHg STANDARD_DEVIATION 9.8704 |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 58 |
| other Total, other adverse events | 18 / 57 | 29 / 58 |
| serious Total, serious adverse events | 0 / 57 | 2 / 58 |
Outcome results
None listed