Trial on the Safety and Efficacy of MLS-101 in Patients With Uncontrolled Hypertension (Target-HTN)

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

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

Study Overview

• Status: Completed
• Conditions: Hypertension, Renal
• Intervention / Treatment: Other: Placebo (Part I); Drug: MLS-101 (Part I); Other: Placebo (Part II); Drug: MLS-101 (Part II)

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Lincoln, California, United States, 95648
      • Site 103
    • Torrance, California, United States, 90502
      • Site 129
    • Tustin, California, United States, 92780
      • Site 135
  • Florida
    • Clearwater, Florida, United States, 33765
      • Site 131
    • Coral Gables, Florida, United States, 33134
      • Site 105
    • Greenacres City, Florida, United States, 33467
      • Site 108
    • Jupiter, Florida, United States, 33458
      • Site 134
    • Miami, Florida, United States, 33126
      • Site 146
    • Miami, Florida, United States, 33135
      • Site 137
    • Miami, Florida, United States, 33135
      • Site 139
    • Miami, Florida, United States, 33144
      • Site 143
    • Pembroke Pines, Florida, United States, 33026
      • Site 122
    • Tampa, Florida, United States, 91303
      • Site 102
  • Georgia
    • Albany, Georgia, United States, 31707
      • Site 118
    • Fayetteville, Georgia, United States, 30214
      • Site 109
    • Lawrenceville, Georgia, United States, 30044
      • Site 125
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Site 136
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
      • Site 138
    • Hammond, Louisiana, United States, 70403
      • Site 154
    • Shreveport, Louisiana, United States, 71105
      • Site 148
    • Slidell, Louisiana, United States, 70458
      • Site 114
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Site 116
    • Saint Louis, Missouri, United States, 63141
      • Site 121
  • Nevada
    • Las Vegas, Nevada, United States, 89121
      • Site 123
  • New York
    • Jamaica, New York, United States, 11432
      • Site 141
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Site 133
    • Charlotte, North Carolina, United States, 28210
      • Site 113
    • Fayetteville, North Carolina, United States, 28304
      • Site 130
    • Greensboro, North Carolina, United States, 27408
      • Site 140
    • Morgantown, North Carolina, United States, 28655
      • Site 104
    • Raleigh, North Carolina, United States, 27612
      • Site 150
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Site 153
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Site 115
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Site 107
    • Kingsport, Tennessee, United States, 37660
      • Site 120
    • Nashville, Tennessee, United States, 37232
      • Site 152
  • Texas
    • Arlington, Texas, United States, 76012
      • Site 151
    • Cypress, Texas, United States, 77429
      • Site 145
    • Dallas, Texas, United States, 75224
      • Site 132
    • McKinney, Texas, United States, 75071
      • Site 124
    • Mesquite, Texas, United States, 75149
      • Site 147
    • Pearland, Texas, United States, 77584
      • Site 126
    • Richland Hills, Texas, United States, 76180
      • Site 128
  • Virginia
    • Forest, Virginia, United States, 24551
      • Site 112

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Part I); Placebo tablet(s) by mouth once or twice daily.	Other: Placebo (Part I); Placebo tablet(s) by mouth once or twice daily.
Experimental: Dose 1 (Part I); MLS-101 tablet(s) by mouth once or twice daily.	Drug: MLS-101 (Part I); MLS-101 tablet(s) by mouth once or twice daily.
Experimental: Dose 2 (Part I); MLS-101 tablet(s) by mouth once or twice daily.	Drug: MLS-101 (Part I); MLS-101 tablet(s) by mouth once or twice daily.
Experimental: Dose 3 (Part I); MLS-101 tablet(s) by mouth once or twice daily.	Drug: MLS-101 (Part I); MLS-101 tablet(s) by mouth once or twice daily.
Placebo Comparator: Placebo (Part II); Placebo tablet(s) by mouth once daily.	Other: Placebo (Part II); Placebo tablet(s) by mouth once daily.
Experimental: Dose (Part II); MLS-101 tablet(s) by mouth once daily.	Drug: MLS-101 (Part II); MLS-101 tablet(s) by mouth once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	8 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	8 Weeks
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.	8 weeks
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.	8 Weeks

Collaborators and Investigators

• Sponsor: Mineralys Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): September 7, 2022
• Study Completion (Actual): October 7, 2022

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: August 11, 2021
• First Posted (Actual): August 12, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Blood pressure; Phase II; Uncontrolled hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hypertension; Hypertension, Renal
• Other Study ID Numbers: MLS-101-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No