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
Brief Title
Trial on the Safety and Efficacy of MLS-101 in Patients With Uncontrolled Hypertension
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hypertension, Renal
Eligibility Criteria
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
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
Inclusion Criteria
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
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
Gender
All
Gender Based
false
Keywords
Blood pressure
Uncontrolled hypertension
Phase II
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05001945
Org Class
Industry
Org Full Name
Mineralys Therapeutics Inc.
Org Study Id
MLS-101-201
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Multicenter Phase 2 Study to Evaluate the Safety, Efficacy, and Tolerability of MLS-101 in Subjects With Uncontrolled Hypertension
Primary Outcomes
Outcome Description
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.
Outcome Measure
Change From Baseline in Office-measured Systolic Blood Pressure (SBP) at Study Week 8 Compared to Placebo
Outcome Time Frame
8 Weeks
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
8 Weeks
Outcome Measure
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)
Outcome Description
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.
Outcome Time Frame
8 weeks
Outcome Measure
Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP)
Outcome Description
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.
Outcome Time Frame
8 Weeks
Outcome Measure
Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Mandeep Kainth
Investigator Email
Investigator Phone