Mineralys 301
Research type
Research Study
Full title
A Randomized, Double-Blind, Placebo Controlled, Parallel Arm, Multicenter Phase 3 Study to Evaluate the Efficacy and Safety of Lorundrostat in Subjects with Uncontrolled and Resistant Hypertension
IRAS ID
1008308
Contact name
Jeffery Fellows
Contact email
Sponsor organisation
Mineralys Therapeutics, Inc
Clinicaltrials.gov Identifier
Research summary
Summary of Research
We are evaluating a new medication called lorundrostat™ in patients with high blood pressure. Lorundrostat blocks the production of aldosterone, which is a hormone that increases blood pressure when its levels are high. Lorundrostat is an investigational (experimental) medicine and has been studied in previous clinical trials which suggest it might be a potential treatment for people with uncontrolled and resistant hypertension.
The purpose of this study is to assess the blood pressure lowering effect of lorundrostat, in combination with prescribed medications, one of which should be a thiazide or thiazide-like diuretic, used for treating high blood pressure. We will evaluate how long the medicine stays detectable in the body and how it may affect other disease markers. Approximately 1000 participants with uncontrolled or resistant hypertension that is not well controlled with their current medications will take part in this study at approximately 200-250 centers globally.
The total duration for each study participant in the study will be 18 weeks with approximately 8-9 study visits. These include a screening period of up to 2 weeks, a run-in period of 2 weeks, a randomised treatment period of 12 weeks and an end of study visit of 2 weeks after last treatment dose. Participants will complete several tests and assessments during these visits including physical examinations, ECGs, blood tests, urine tests and blood pressure measurements
Participants will be randomly assigned (like flipping a coin) to receive tablets containing either lorundrostat or placebo (dummy drug) to be taken once daily in addition to their prescribed antihypertensive (AHT) medications used for treating high blood pressure.
Participants may be asked to take part in an open-label extension study after the 12-week treatment phase. If they take part in the open-label extension their participation in this study will be 16 weeks.
Summary of Results
Report Date: 07Jan26
Participants per country: United States 867, Australia 35 Bulgaria 31 Canda 3 France 1 Germany 13 Italy 19 Netherlands 2 Poland 48 Romania 21 Spain 15 GB 38
Study Conducted: November 2023 to January 2025Main Objective of this Study
The purpose of this Phase 3 trial was to determine if participants with high blood pressure and who were already taking 2 to 5 blood pressure lowering medicines would have lower blood pressure BP after taking lorundrostat 50 mg for 6 weeks compared to taking placebo a tablet that looks like lorundrostat but contains no drugStudy Demographics
Average age: 61.6 years
46.9% female; 53.1% male
67.7% White/Caucasian
28.7% Black/African American
3.6% American Indian or Pacific IslanderCriteria for selecting participants
Inclusion
At least 18 years old
The participant has high blood pressure.
Taking 2 to 5 blood pressure medicines
History of high blood pressure lasting at least 6 months
BMI Body Mass Index of ≥18 kg/m2Exclusion
Women who are pregnant, plan to become pregnant, or are breastfeeding
Participation in a trial involving any investigational device or small-molecule drug within 4 weeks or 6 months for biologic antibody drugs prior to the Screening Visit
Poor Kidney Function
High Serum potassium
Low Serum sodium
History of heart failure, heart attack, stroke, or temporary mini stroke within 6 months.What is lorundrostat
Lorundrostat an aldosterone synthase inhibitor is being investigated as a potential treatment to help lower blood pressure when other treatments don’t work well. It is taken by mouth. It works by blocking an enzyme, which makes a hormone called aldosterone. This hormone can raise blood pressure, so lowering it helps keep blood pressure under control.Treatment Groups:
1083 participants were in the trial. The treatment period lasted 12 weeks. Participants were randomized into 3 treatment groups. Randomization was assigned by chance. This helps to make the groups equal by reducing differences between the groups.
Treatment Group 1: lorundrostat 50mg and then 100mg - 270 Participants
Treatment Group 2: lorundrostat 50mg - 538 Participants
Treatment Group 3: Placebo - 270 Participants
Participants were blinded to the treatment group which means they did not know if they were receiving lorundrostat or placebo.
The trial data supports the use of lorundrostat as a treatment option for participants with high blood pressure.Side Effects
Researchers recorded any side effects that happened in participants. Side effects are unfavourable medical occurrences in a trial participant where there is a possible causal relationship between the side effect and the new drug. 1 participant in the placebo group died after week 6 unrelated to lorundrostat.Number of participants who experienced side effects (adverse events of special interest) is listed below according to assigned treatment group (Placebo, Lorundrostat 50mg, Lorundrostat 50mg to 100mg) respectively:
High Blood Pressure SBP ≥ 180 or DBP ≥ 110: 11; 10; 2 participants
Low Blood Pressure with symptoms 1; 11; 5 participants
High Potassium 1; 11; 7 participants
Low Sodium 9; 37; 28 participants
Hormone Changes 3; 0; 0 participants
Poor Kidney Function 2; 16; 9 participantsStudy Results
Overall, the trial showed that lorundrostat helped lower blood pressure and was well tolerated.
When added to other standard blood pressure medicines, lorundrostat 50 mg once daily lowered blood pressure by 16.9mmHg after 6 weeks and about 19mmHg after 12 weeks compared to blood pressure readings taken at the beginning of the trial before lorundrostat was started. These improvements were seen across all groups regardless of demographics or other medications.
Lorundrostat was generally safe and well tolerated. Less than 1% of people stopped treatment because of side effects.How has the study helped people with high blood pressure?
In the trial, lorundrostat lowered the blood pressure for participants already using 2 to 5 blood pressure medicines, and for participants of different demographics and BMIs.
Limitations: Lorundrostat compared with placebo was evaluated for 12 weeks, while outside of a clinical trial, people take high blood pressure medicines for longer.
Important Note: The outcome of 1 trial reflects only 1 single clinical trial. Other trials may show something different either already done or future studies.Follow-up studies
Participants from this trial may be able to continue treatment with lorundrostat for at least 12 months in the MLS-101-901: An Open-Label Extension Study to Assess Long-Term Safety, Efficacy, and Tolerability of Lorundrostat in Subjects with Hypertension.Further Information
Manish Saxena, MBBS: Luke Laffin, MD; Claudio Borghi, MD, et al;
Lorundrostat in Participants With Uncontrolled Hypertension and Treatment-Resistant Hypertension. JAMA 2025;334;(5):409-418. doi:10.1001/jama.2025.9413REC name
London - Dulwich Research Ethics Committee
REC reference
23/LO/0995
Date of REC Opinion
24 Jan 2024
REC opinion
Further Information Favourable Opinion