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

Hypertension, Renal Clinical Trial

— Target-HTN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05001945
• Other study ID #: MLS-101-201
• Status: Completed
• Phase: Phase 2
• Start date: July 1, 2021
• Est. completion date: October 7, 2022

Study information

• Verified date: January 2024
• Source: Mineralys Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: October 7, 2022
• Est. primary completion date: September 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Renal

Intervention

Drug:
• MLS-101 (Part I)
MLS-101 tablet(s) by mouth once or twice daily.

Other:
• Placebo (Part I)
Placebo tablet(s) by mouth once or twice daily.
• Placebo (Part II)
Placebo tablet(s) by mouth once daily.

Drug:
• MLS-101 (Part II)
MLS-101 tablet(s) by mouth once daily.

Locations

Country	Name	City	State
United States	Site 118	Albany	Georgia
United States	Site 151	Arlington	Texas
United States	Site 136	Arlington Heights	Illinois
United States	Site 133	Asheboro	North Carolina
United States	Site 138	Bossier City	Louisiana
United States	Site 113	Charlotte	North Carolina
United States	Site 107	Chattanooga	Tennessee
United States	Site 131	Clearwater	Florida
United States	Site 153	Cleveland	Ohio
United States	Site 105	Coral Gables	Florida
United States	Site 145	Cypress	Texas
United States	Site 132	Dallas	Texas
United States	Site 109	Fayetteville	Georgia
United States	Site 130	Fayetteville	North Carolina
United States	Site 112	Forest	Virginia
United States	Site 108	Greenacres City	Florida
United States	Site 140	Greensboro	North Carolina
United States	Site 154	Hammond	Louisiana
United States	Site 141	Jamaica	New York
United States	Site 116	Jefferson City	Missouri
United States	Site 134	Jupiter	Florida
United States	Site 120	Kingsport	Tennessee
United States	Site 123	Las Vegas	Nevada
United States	Site 125	Lawrenceville	Georgia
United States	Site 103	Lincoln	California
United States	Site 124	McKinney	Texas
United States	Site 147	Mesquite	Texas
United States	Site 137	Miami	Florida
United States	Site 139	Miami	Florida
United States	Site 143	Miami	Florida
United States	Site 146	Miami	Florida
United States	Site 104	Morgantown	North Carolina
United States	Site 152	Nashville	Tennessee
United States	Site 126	Pearland	Texas
United States	Site 122	Pembroke Pines	Florida
United States	Site 150	Raleigh	North Carolina
United States	Site 115	Rapid City	South Dakota
United States	Site 128	Richland Hills	Texas
United States	Site 121	Saint Louis	Missouri
United States	Site 148	Shreveport	Louisiana
United States	Site 114	Slidell	Louisiana
United States	Site 102	Tampa	Florida
United States	Site 129	Torrance	California
United States	Site 135	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Mineralys Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	8 Weeks
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.	8 Weeks
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.	8 weeks
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.	8 Weeks