Hypertension, Renal
Conditions
Keywords
Blood pressure, Uncontrolled hypertension, Phase II
Brief summary
A randomized, double-blind, placebo-controlled, dose-ranging, Phase II study to evaluate the safety, efficacy, and tolerability of MLS-101 in Subjects With Uncontrolled Hypertension
Interventions
DRUGMLS-101 (Part I)
MLS-101 tablet(s) by mouth once or twice daily.
OTHERPlacebo (Part I)
Placebo tablet(s) by mouth once or twice daily.
OTHERPlacebo (Part II)
Placebo tablet(s) by mouth once daily.
DRUGMLS-101 (Part II)
MLS-101 tablet(s) by mouth once daily.
Sponsors
Mineralys Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and nonpregnant, nonlactating female subjects ≥ 18 years of age. 2. Written informed consent Health Insurance Portability and Accountability Act authorization, and local patient privacy required documentation for this study have been obtained 3. Automated office blood pressure (AOBP) with SBP ≥ 130 mm Hg 4. Background antihypertensive treatment of ≥ 2 drugs 5. Serum cortisol ≥ 18 mcg/dL
Exclusion criteria
1\. Concomitant use of epithelial sodium channel inhibitors or mineralocorticoid receptor antagonists 3\. Subjects with hypokalemia 4\. Subjects with hyperkalemia 5\. Subjects with serum cortisol \< 3 mcg/dL 6\. Subjects with serum sodium \< 135 mEq/L 7\. Subjects with estimated glomerular filtration rate \< 60 mL/min/1.73m2 8\. Subjects with type 1 or uncontrolled (hemoglobin A1c ≥ 9%) type 2 diabetes mellitus 9\. Subjects with body mass index \> 40 kg/m2 10\. Subjects with unstable angina 11\. Subjects with SBP ≥ 175 mm Hg or DBP ≥ 100 mm Hg for Part 1 and SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg for Part 2 at Pre-Screening, Screening/Start of Placebo Run-in, or Randomization 12\. Subjects with a decrease in SBP ≥ 20 mm Hg or DBP ≥ 10 mm Hg from sitting to standing position at screening 13\. Subjects who, in the opinion of the investigator, have suspected nonadherence to antihypertensive treatment 14\. Subjects who, in the opinion of the investigator, have any major medical illness or symptoms 15\. Subjects who, in the opinion of the investigator, have any acute or chronic medical or psychiatric condition 16\. Subjects undergoing treatment with any of the following medications: 1. Topical corticoids 2. Sympathomimetic decongestants 3. Theophylline 4. Phosphodiesterase type 5 inhibitors 5. NSAIDs 6. Intramuscular steroids 7. Estrogen 8. Cytochromes 9. Strong CYP3A and CYP3A4 inducers 17\. Subjects with known hypersensitivity to MLS-101 or any of the excipients 18\. Subjects who are night-shift workers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo | 8 Weeks | The primary outcome was defined as the change in office-measured (mean of last 2 of 5 unattended measurements using an automated oscillometric sphygmomanometer device after approximately 5 minutes of rest in the seated position) SBP from baseline to the end of Study Week 8. The primary efficacy analysis was performed using a mixed model repeated measures (MMRM) approach with defined fixed effects per the statistical analysis plan. A least-square estimate of the mean difference between each dose group and the placebo group is provided for Week 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | 8 Weeks | The ABPM SBP was measured at baseline and EoT. Change in ABPM-derived mean SBP and DBP from baseline to EoT was analyzed using an ANCOVA with a term for treatment group and a baseline mean 24-hour value as a covariate. |
| Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP) | 8 weeks | Change in office-measured (average of last 2 of 5 unattended measurements using an automated oscillometric sphygmomanometer device after approximately 5 minutes of rest in the seated position) DBP from baseline to the end of study at week 8. |
| Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8 | 8 Weeks | Each participant was assessed as a success if the Week 8 value for SBP was ≤130 mmHg and DBP ≤80 mmHg; subjects not meeting both these thresholds were assessed as a failure. Subjects missing an assessment at Week 8 or who received rescue medications were also considered failures. |
Countries
United States
Participant flow
Pre-assignment details
After successful screening, subjects with plasma renin activity (PRA) ≤1ng/mL/h began a single-blind (SB) run-in period of BID oral treatment with placebo (PBO) in Part 1, and subjects with PRA \>1ng/mL/h began a SB QD oral treatment with PBO in Part 2, while continuing on stable doses of background AHT medications. Subjects returned 2 weeks later on Day 1, and those who continued to meet eligibility requirements were randomized in 1:1 fashion with PBO (Part 1), or 6:1 fashion with PBO (Part 2).
Participants by arm
| Arm | Count |
|---|---|
| Placebo - Part 1 Participants received matching placebo, taken orally, for 8 weeks in Part 1 of the study | 30 |
| Lorundrostat 12.5 mg BID - Part 1 Participants received 12.5 mg of lorundrostat twice daily, taken orally, for 8 weeks in Part 1 of the study | 22 |
| Lorundrostat 25 mg BID - Part 1 Participants received 25 mg of lorundrostat twice daily, taken orally, for 8 weeks in Part 1 of the study | 30 |
| Lorundrostat 12.5 mg QD - Part 1 Participants received 12.5 mg of lorundrostat once daily, taken orally, for 8 weeks in Part 1 of the study | 23 |
| Lorundrostat 50 mg QD - Part 1 Participants received 50 mg of lorundrostat once daily, taken orally, for 8 weeks in Part 1 of the study | 28 |
| Lorundrostat 100 mg QD - Part 1 Participants received 100 mg of lorundrostat once daily, taken orally, for 8 weeks in Part 1 of the study | 30 |
| Placebo - Part 2 Participants received matching placebo, taken orally, for 8 weeks in Part 2 of the study | 6 |
| Lorundrostat 100 mg QD - Part 2 Participants received 100 mg of lorundrostat once daily, taken orally, for 8 weeks in Part 2 of the study | 31 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 2 | 0 | 1 | 0 | 0 |
| Overall Study | Not specified by Investigator | 0 | 3 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Lorundrostat 12.5 mg BID - Part 1 | Lorundrostat 25 mg BID - Part 1 | Lorundrostat 12.5 mg QD - Part 1 | Lorundrostat 50 mg QD - Part 1 | Placebo - Part 1 | Lorundrostat 100 mg QD - Part 1 | Placebo - Part 2 | Lorundrostat 100 mg QD - Part 2 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 10.1 | 64.8 years STANDARD_DEVIATION 9.7 | 65.2 years STANDARD_DEVIATION 11.3 | 64.7 years STANDARD_DEVIATION 9.5 | 62.6 years STANDARD_DEVIATION 10.7 | 68.7 years STANDARD_DEVIATION 8.9 | 62.7 years STANDARD_DEVIATION 12.3 | 66.6 years STANDARD_DEVIATION 10.6 | 65.7 years STANDARD_DEVIATION 10.2 |
| Age, Customized <65 | 6 Participants | 14 Participants | 10 Participants | 15 Participants | 17 Participants | 9 Participants | 4 Participants | 8 Participants | 83 Participants |
| Age, Customized 65-79 | 13 Participants | 15 Participants | 10 Participants | 13 Participants | 12 Participants | 17 Participants | 2 Participants | 22 Participants | 104 Participants |
| Age, Customized >=80 | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 13 Participants |
| Body Mass Index | 32 kg/m^2 STANDARD_DEVIATION 5.2 | 30.6 kg/m^2 STANDARD_DEVIATION 5.5 | 30.6 kg/m^2 STANDARD_DEVIATION 4.9 | 32.0 kg/m^2 STANDARD_DEVIATION 5 | 31.9 kg/m^2 STANDARD_DEVIATION 4.9 | 30.4 kg/m^2 STANDARD_DEVIATION 5.5 | 32.0 kg/m^2 STANDARD_DEVIATION 3.9 | 30.5 kg/m^2 STANDARD_DEVIATION 4.4 | 31.1 kg/m^2 STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 17 Participants | 10 Participants | 14 Participants | 12 Participants | 16 Participants | 2 Participants | 17 Participants | 95 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 13 Participants | 12 Participants | 14 Participants | 18 Participants | 13 Participants | 4 Participants | 12 Participants | 101 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 7 Participants | 11 Participants | 8 Participants | 16 Participants | 15 Participants | 2 Participants | 6 Participants | 72 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 15 Participants | 23 Participants | 11 Participants | 19 Participants | 13 Participants | 14 Participants | 4 Participants | 25 Participants | 124 Participants |
| Region of Enrollment United States | 22 participants | 30 participants | 23 participants | 28 participants | 30 participants | 30 participants | 6 participants | 31 participants | 200 participants |
| Seated Automated Office-measured Diastolic Blood Pressure | 81.6 mmHg STANDARD_DEVIATION 9.4 | 80.1 mmHg STANDARD_DEVIATION 9.3 | 80.3 mmHg STANDARD_DEVIATION 12 | 84.7 mmHg STANDARD_DEVIATION 7 | 83.8 mmHg STANDARD_DEVIATION 9.5 | 78.5 mmHg STANDARD_DEVIATION 10 | 81.5 mmHg STANDARD_DEVIATION 7.9 | 78.6 mmHg STANDARD_DEVIATION 10 | 81.1 mmHg STANDARD_DEVIATION 9.7 |
| Seated Automated Office-measured Systolic Blood Pressure | 142.6 mmHg STANDARD_DEVIATION 13.3 | 142.8 mmHg STANDARD_DEVIATION 13.1 | 142.9 mmHg STANDARD_DEVIATION 13.7 | 140.0 mmHg STANDARD_DEVIATION 12.1 | 142.9 mmHg STANDARD_DEVIATION 10.7 | 142.2 mmHg STANDARD_DEVIATION 13.4 | 135.3 mmHg STANDARD_DEVIATION 5.5 | 139.8 mmHg STANDARD_DEVIATION 9.1 | 141.6 mmHg STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 14 Participants | 19 Participants | 12 Participants | 15 Participants | 17 Participants | 18 Participants | 4 Participants | 21 Participants | 120 Participants |
| Sex: Female, Male Male | 8 Participants | 11 Participants | 11 Participants | 13 Participants | 13 Participants | 12 Participants | 2 Participants | 10 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 22 | 0 / 30 | 0 / 23 | 0 / 28 | 0 / 30 | 0 / 6 | 0 / 31 | 0 / 305 |
| other Total, other adverse events | 7 / 30 | 13 / 22 | 18 / 30 | 16 / 23 | 10 / 28 | 16 / 30 | 1 / 6 | 19 / 31 | 8 / 305 |
| serious Total, serious adverse events | 0 / 30 | 0 / 22 | 0 / 30 | 2 / 23 | 0 / 28 | 0 / 30 | 0 / 6 | 1 / 31 | 0 / 305 |
Outcome results
Primary
Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo
The primary outcome was defined as the change in office-measured (mean of last 2 of 5 unattended measurements using an automated oscillometric sphygmomanometer device after approximately 5 minutes of rest in the seated position) SBP from baseline to the end of Study Week 8. The primary efficacy analysis was performed using a mixed model repeated measures (MMRM) approach with defined fixed effects per the statistical analysis plan. A least-square estimate of the mean difference between each dose group and the placebo group is provided for Week 8.
Time frame: 8 Weeks
Population: The full analysis set included all randomized subjects who received at least 1 dose of randomized study treatment (lorundrostat or placebo). Subjects were analyzed according to the randomized study treatment group.~Per the study SAP, modelled analysis comparisons for Part 2 were performed for 100 mg QD Part 2 vs 100mg QD Part 1, and not to Placebo - Part 2. Accordingly, while subjects were analyzed, modelled LSmeans for Placebo - Part 2 were not reported.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Part 1 | Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo | -4.10 mmHg | Standard Error 2.62 |
| Lorundrostat 12.5 mg BID - Part 1 | Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo | -11.3 mmHg | Standard Error 3.15 |
| Lorundrostat 25 mg BID - Part 1 | Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo | -11.07 mmHg | Standard Error 2.65 |
| Lorundrostat 12.5 mg QD - Part 1 | Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo | -5.63 mmHg | Standard Error 3.16 |
| Lorundrostat 50 mg QD - Part 1 | Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo | -13.69 mmHg | Standard Error 2.67 |
| Lorundrostat 100 mg QD - Part 1 | Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo | -11.92 mmHg | Standard Error 2.77 |
| Lorundrostat 100 mg QD - Part 2 | Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo | -11.43 mmHg | Standard Error 2.41 |
Secondary
Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT)
The ABPM SBP was measured at baseline and EoT. Change in ABPM-derived mean SBP and DBP from baseline to EoT was analyzed using an ANCOVA with a term for treatment group and a baseline mean 24-hour value as a covariate.
Time frame: 8 Weeks
Population: The full analysis set included all randomized subjects who received at least 1 dose of randomized study treatment (lorundrostat or placebo). Subjects were analyzed according to the randomized study treatment group.~Per the study SAP, modelled analysis comparisons for Part 2 were performed for 100 mg QD Part 2 vs 100mg QD Part 1, and not to Placebo - Part 2. Accordingly, while subjects were analyzed, modelled LSmeans for Placebo - Part 2 were not reported.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean SBP | -1.01 mmHg | Standard Error 2.38 |
| Placebo - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean DBP | -0.90 mmHg | Standard Error 1.46 |
| Lorundrostat 12.5 mg BID - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean SBP | -5.78 mmHg | Standard Error 3.03 |
| Lorundrostat 12.5 mg BID - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean DBP | -5.14 mmHg | Standard Error 1.85 |
| Lorundrostat 25 mg BID - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean SBP | -9.05 mmHg | Standard Error 2.38 |
| Lorundrostat 25 mg BID - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean DBP | -6.03 mmHg | Standard Error 1.45 |
| Lorundrostat 12.5 mg QD - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean SBP | -2.51 mmHg | Standard Error 3.15 |
| Lorundrostat 12.5 mg QD - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean DBP | -2.34 mmHg | Standard Error 1.91 |
| Lorundrostat 50 mg QD - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean SBP | -4.86 mmHg | Standard Error 2.34 |
| Lorundrostat 50 mg QD - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean DBP | -3.64 mmHg | Standard Error 1.4 |
| Lorundrostat 100 mg QD - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean SBP | -6.34 mmHg | Standard Error 2.5 |
| Lorundrostat 100 mg QD - Part 1 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean DBP | -6.14 mmHg | Standard Error 1.51 |
| Lorundrostat 100 mg QD - Part 2 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean SBP | -1.02 mmHg | Standard Error 2.64 |
| Lorundrostat 100 mg QD - Part 2 | Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean Systolic Blood Pressure (SBP) and Mean Diastolic Blood Pressure (DBP) From Baseline to End of Treatment (EoT) | Mean DBP | -0.07 mmHg | Standard Error 1.69 |
Secondary
Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8
Each participant was assessed as a success if the Week 8 value for SBP was ≤130 mmHg and DBP ≤80 mmHg; subjects not meeting both these thresholds were assessed as a failure. Subjects missing an assessment at Week 8 or who received rescue medications were also considered failures.
Time frame: 8 Weeks
Population: The full analysis set included all randomized subjects who received at least 1 dose of randomized study treatment (lorundrostat or placebo). Subjects were analyzed according to the randomized study treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo - Part 1 | Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8 | 7 Participants |
| Lorundrostat 12.5 mg BID - Part 1 | Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8 | 7 Participants |
| Lorundrostat 25 mg BID - Part 1 | Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8 | 13 Participants |
| Lorundrostat 12.5 mg QD - Part 1 | Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8 | 6 Participants |
| Lorundrostat 50 mg QD - Part 1 | Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8 | 12 Participants |
| Lorundrostat 100 mg QD - Part 1 | Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8 | 9 Participants |
| Placebo - Part 2 | Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8 | 3 Participants |
| Lorundrostat 100 mg QD - Part 2 | Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8 | 17 Participants |
Secondary
Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP)
Change in office-measured (average of last 2 of 5 unattended measurements using an automated oscillometric sphygmomanometer device after approximately 5 minutes of rest in the seated position) DBP from baseline to the end of study at week 8.
Time frame: 8 weeks
Population: The full analysis set included all randomized subjects who received at least 1 dose of randomized study treatment (lorundrostat or placebo). Subjects were analyzed according to the randomized study treatment group.~Per the study SAP, modelled analysis comparisons for Part 2 were performed for 100 mg QD Part 2 vs 100mg QD Part 1, and not to Placebo - Part 2. Accordingly, while subjects were analyzed, modelled LSmeans for Placebo - Part 2 were not reported.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Part 1 | Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP) | -1.63 mmHg | Standard Error 1.66 |
| Lorundrostat 12.5 mg BID - Part 1 | Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP) | -5.47 mmHg | Standard Error 2.02 |
| Lorundrostat 25 mg BID - Part 1 | Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP) | -4.12 mmHg | Standard Error 1.68 |
| Lorundrostat 12.5 mg QD - Part 1 | Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP) | -3.76 mmHg | Standard Error 2.02 |
| Lorundrostat 50 mg QD - Part 1 | Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP) | -7.09 mmHg | Standard Error 1.7 |
| Lorundrostat 100 mg QD - Part 1 | Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP) | -5.75 mmHg | Standard Error 1.77 |
| Lorundrostat 100 mg QD - Part 2 | Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP) | -5.55 mmHg | Standard Error 1.42 |