Trial on the Safety and Efficacy of MLS-101 in Patients With Uncontrolled Hypertension
- Conditions
- Hypertension, Renal
- Interventions
- Other: Placebo (Part I)Drug: MLS-101 (Part I)Other: Placebo (Part II)Drug: MLS-101 (Part II)
- Registration Number
- NCT05001945
- Lead Sponsor
- Mineralys Therapeutics Inc.
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 200
- Male and nonpregnant, nonlactating female subjects ≥ 18 years of age.
- Written informed consent Health Insurance Portability and Accountability Act authorization, and local patient privacy required documentation for this study have been obtained
- Automated office blood pressure (AOBP) with SBP ≥ 130 mm Hg
- Background antihypertensive treatment of ≥ 2 drugs
- Serum cortisol ≥ 18 mcg/dL
-
Concomitant use of epithelial sodium channel inhibitors or mineralocorticoid receptor antagonists
-
Subjects with hypokalemia
-
Subjects with hyperkalemia
-
Subjects with serum cortisol < 3 mcg/dL
-
Subjects with serum sodium < 135 mEq/L
-
Subjects with estimated glomerular filtration rate < 60 mL/min/1.73m2
-
Subjects with type 1 or uncontrolled (hemoglobin A1c ≥ 9%) type 2 diabetes mellitus
-
Subjects with body mass index > 40 kg/m2
-
Subjects with unstable angina
-
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
-
Subjects with a decrease in SBP ≥ 20 mm Hg or DBP ≥ 10 mm Hg from sitting to standing position at screening
-
Subjects who, in the opinion of the investigator, have suspected nonadherence to antihypertensive treatment
-
Subjects who, in the opinion of the investigator, have any major medical illness or symptoms
-
Subjects who, in the opinion of the investigator, have any acute or chronic medical or psychiatric condition
-
Subjects undergoing treatment with any of the following medications:
-
Topical corticoids
-
Sympathomimetic decongestants
-
Theophylline
-
Phosphodiesterase type 5 inhibitors
-
NSAIDs
-
Intramuscular steroids
-
Estrogen
-
Cytochromes
-
Strong CYP3A and CYP3A4 inducers
-
Subjects with known hypersensitivity to MLS-101 or any of the excipients
-
Subjects who are night-shift workers
-
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo (Part I) Placebo (Part I) Placebo tablet(s) by mouth once or twice daily. Dose 1 (Part I) MLS-101 (Part I) MLS-101 tablet(s) by mouth once or twice daily. Dose 3 (Part I) MLS-101 (Part I) MLS-101 tablet(s) by mouth once or twice daily. Placebo (Part II) Placebo (Part II) Placebo tablet(s) by mouth once daily. Dose 2 (Part I) MLS-101 (Part I) MLS-101 tablet(s) by mouth once or twice daily. Dose (Part II) MLS-101 (Part II) MLS-101 tablet(s) by mouth once daily.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (44)
Site 122
🇺🇸Pembroke Pines, Florida, United States
Site 120
🇺🇸Kingsport, Tennessee, United States
Site 146
🇺🇸Miami, Florida, United States
Site 137
🇺🇸Miami, Florida, United States
Site 139
🇺🇸Miami, Florida, United States
Site 143
🇺🇸Miami, Florida, United States
Site 123
🇺🇸Las Vegas, Nevada, United States
Site 152
🇺🇸Nashville, Tennessee, United States
Site 103
🇺🇸Lincoln, California, United States
Site 129
🇺🇸Torrance, California, United States
Site 145
🇺🇸Cypress, Texas, United States
Site 136
🇺🇸Arlington Heights, Illinois, United States
Site 125
🇺🇸Lawrenceville, Georgia, United States
Site 130
🇺🇸Fayetteville, North Carolina, United States
Site 118
🇺🇸Albany, Georgia, United States
Site 150
🇺🇸Raleigh, North Carolina, United States
Site 113
🇺🇸Charlotte, North Carolina, United States
Site 133
🇺🇸Asheboro, North Carolina, United States
Site 114
🇺🇸Slidell, Louisiana, United States
Site 140
🇺🇸Greensboro, North Carolina, United States
Site 124
🇺🇸McKinney, Texas, United States
Site 121
🇺🇸Saint Louis, Missouri, United States
Site 135
🇺🇸Tustin, California, United States
Site 132
🇺🇸Dallas, Texas, United States
Site 147
🇺🇸Mesquite, Texas, United States
Site 109
🇺🇸Fayetteville, Georgia, United States
Site 104
🇺🇸Morgantown, North Carolina, United States
Site 153
🇺🇸Cleveland, Ohio, United States
Site 151
🇺🇸Arlington, Texas, United States
Site 126
🇺🇸Pearland, Texas, United States
Site 112
🇺🇸Forest, Virginia, United States
Site 128
🇺🇸Richland Hills, Texas, United States
Site 116
🇺🇸Jefferson City, Missouri, United States
Site 102
🇺🇸Tampa, Florida, United States
Site 138
🇺🇸Bossier City, Louisiana, United States
Site 148
🇺🇸Shreveport, Louisiana, United States
Site 107
🇺🇸Chattanooga, Tennessee, United States
Site 105
🇺🇸Coral Gables, Florida, United States
Site 134
🇺🇸Jupiter, Florida, United States
Site 108
🇺🇸Greenacres City, Florida, United States
Site 154
🇺🇸Hammond, Louisiana, United States
Site 131
🇺🇸Clearwater, Florida, United States
Site 115
🇺🇸Rapid City, South Dakota, United States
Site 141
🇺🇸Jamaica, New York, United States