Trial on the Safety and Efficacy of MLS-101 in Patients With Uncontrolled Hypertension

NCT05001945 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: MLS-101-201
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 44

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

Conditions

Hypertension, Renal

Keywords

Blood pressure; Uncontrolled hypertension; Phase II

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

• Week 8 Change From Baseline in Office-measured Diastolic Blood Pressure (DBP)

  8 weeks

• Number of Participants With Blood Pressure ≤ 130/80 mmHg at Week 8

  8 Weeks

Study Arms (6)

Placebo (Part I)

PLACEBO COMPARATOR

Placebo tablet(s) by mouth once or twice daily.

Other: Placebo (Part I)

Dose 1 (Part I)

EXPERIMENTAL

MLS-101 tablet(s) by mouth once or twice daily.

Drug: MLS-101 (Part I)

Dose 2 (Part I)

EXPERIMENTAL

MLS-101 tablet(s) by mouth once or twice daily.

Drug: MLS-101 (Part I)

Dose 3 (Part I)

EXPERIMENTAL

MLS-101 tablet(s) by mouth once or twice daily.

Drug: MLS-101 (Part I)

Placebo (Part II)

PLACEBO COMPARATOR

Placebo tablet(s) by mouth once daily.

Other: Placebo (Part II)

Dose (Part II)

EXPERIMENTAL

MLS-101 tablet(s) by mouth once daily.

Drug: MLS-101 (Part II)

Interventions

MLS-101 (Part I) DRUG

MLS-101 tablet(s) by mouth once or twice daily.

Dose 1 (Part I); Dose 2 (Part I); Dose 3 (Part I)

Placebo (Part I) OTHER

Placebo tablet(s) by mouth once or twice daily.

Placebo (Part I)

Placebo (Part II) OTHER

Placebo tablet(s) by mouth once daily.

Placebo (Part II)

MLS-101 (Part II) DRUG

MLS-101 tablet(s) by mouth once daily.

Dose (Part II)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \. 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:

Sponsors & Collaborators

• Mineralys Therapeutics Inc.: lead

Study Sites (44)

Site 103

Lincoln, California, 95648, United States

Location

Site 129

Torrance, California, 90502, United States

Location

Site 135

Tustin, California, 92780, United States

Location

Site 131

Clearwater, Florida, 33765, United States

Location

Site 105

Coral Gables, Florida, 33134, United States

Location

Site 108

Greenacres City, Florida, 33467, United States

Location

Site 134

Jupiter, Florida, 33458, United States

Location

Site 146

Miami, Florida, 33126, United States

Location

Site 137

Miami, Florida, 33135, United States

Location

Site 139

Miami, Florida, 33135, United States

Location

Site 143

Miami, Florida, 33144, United States

Location

Site 122

Pembroke Pines, Florida, 33026, United States

Location

Site 102

Tampa, Florida, 91303, United States

Location

Site 118

Albany, Georgia, 31707, United States

Location

Site 109

Fayetteville, Georgia, 30214, United States

Location

Site 125

Lawrenceville, Georgia, 30044, United States

Location

Site 136

Arlington Heights, Illinois, 60005, United States

Location

Site 138

Bossier City, Louisiana, 71111, United States

Location

Site 154

Hammond, Louisiana, 70403, United States

Location

Site 148

Shreveport, Louisiana, 71105, United States

Location

Site 114

Slidell, Louisiana, 70458, United States

Location

Site 116

Jefferson City, Missouri, 65109, United States

Location

Site 121

St Louis, Missouri, 63141, United States

Location

Site 123

Las Vegas, Nevada, 89121, United States

Location

Site 141

Jamaica, New York, 11432, United States

Location

Site 133

Asheboro, North Carolina, 27203, United States

Location

Site 113

Charlotte, North Carolina, 28210, United States

Location

Site 130

Fayetteville, North Carolina, 28304, United States

Location

Site 140

Greensboro, North Carolina, 27408, United States

Location

Site 104

Morgantown, North Carolina, 28655, United States

Location

Site 150

Raleigh, North Carolina, 27612, United States

Location

Site 153

Cleveland, Ohio, 44195, United States

Location

Site 115

Rapid City, South Dakota, 57702, United States

Location

Site 107

Chattanooga, Tennessee, 37421, United States

Location

Site 120

Kingsport, Tennessee, 37660, United States

Location

Site 152

Nashville, Tennessee, 37232, United States

Location

Site 151

Arlington, Texas, 76012, United States

Location

Site 145

Cypress, Texas, 77429, United States

Location

Site 132

Dallas, Texas, 75224, United States

Location

Site 124

McKinney, Texas, 75071, United States

Location

Site 147

Mesquite, Texas, 75149, United States

Location

Site 126

Pearland, Texas, 77584, United States

Location

Site 128

Richland Hills, Texas, 76180, United States

Location

Site 112

Forest, Virginia, 24551, United States

Location

Related Publications (1)

• Laffin LJ, Rodman D, Luther JM, Vaidya A, Weir MR, Rajicic N, Slingsby BT, Nissen SE; Target-HTN Investigators. Aldosterone Synthase Inhibition With Lorundrostat for Uncontrolled Hypertension: The Target-HTN Randomized Clinical Trial. JAMA. 2023 Sep 26;330(12):1140-1150. doi: 10.1001/jama.2023.16029.

  PMID: 37690061 DERIVED

MeSH Terms

Conditions

Hypertension, Renal

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

Following the completion of the planned interim analysis in January 2022, the two lowest doses in Part 1 (i.e., 12.5 mg QD and 12.5 mg BID) were dropped from the study and no further subjects were enrolled in these treatment arms. Accordingly, overall subject numbers in these arms is less than originally planned.

Results Point of Contact

• Title: David Rodman, MD Chief Medical Officer
• Organization: Mineralys Therapeutics

drodman@mineralystx.com

1-888-378-6240

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: August 12, 2021
• Study Start: July 1, 2021
• Primary Completion: September 7, 2022
• Study Completion: October 7, 2022
• Last Updated: January 5, 2024
• Results First Posted: January 5, 2024

Record last verified: 2024-01

Locations

US (44)