PRECISION
Research type
Research Study
Full title
Multi-center, blinded, randomized, parallel-group, Phase 3 study with aprocitentan in subjects with Resistant Hypertension (RHT)
IRAS ID
226923
Contact name
David John Webb
Contact email
Sponsor organisation
Idorsia Pharmaceuticals Ltd
Eudract number
2017-004393-33
Clinicaltrials.gov Identifier
NA, NA
Duration of Study in the UK
2 years, 4 months, 23 days
Research summary
Research Summary
This Study is being performed to learn more about the safety and effects of the investigational study drug, Aprocitentan, in the treatment of difficult to control (resistant) high blood pressure (hypertension). It is hoped that this study drug will lower blood pressure of patients with difficult to control (resistant) high blood pressure (hypertension) and keep their blood pressure reduced for a long period of time.
It is important to compare aprocitentan with a placebo to show that aprocitentan itself actually reduces blood pressure. Placebo looks like real medicine but has no active drug in it. Nevertheless, it can influence blood pressure.
There will be approximately 600 people participating in this study from approximately 100 clinics in about 20 countries worldwide. Each patient will be in the study for up to 17 months which includes:
• A screening period of 4 to 12 weeks: Basic medical tests will be done at the start to confirm potential subjects are suitable for the study. During the screening period, participants will be asked to switch from their usual blood pressure medicines to a standard one provided by the sponsor (combination of amlodipine, valsartan and hydrochlorothiazide, which is referred to as the background therapy).
If during the screening period, the participant does not fit all of the entry criteria on the first try, they can be re-tested once.
• A treatment period of up to 1 year: during which time participants will be taking study drug (aprocitentan or placebo). More tests will be performed while they are taking the study drug
• A follow-up period: A final safety check-up will be performed approximately 30 days after the participant has finished taking the study drug to check their health which is either performed onsite or over the telephone.
The study is being funded by Idorsia Pharmaceuticals Limited.Summary of Results
The goal of this study was to show the blood pressure lowering effect of aprocitentan. In the study some patients took placebo as a study medication (the placebo was a tablet that looks exactly like the aprocitentan tablet but did not contain active substance) for short periods. Placebo periods in the study allowed researchers to analyse the efficacy of aprocitentan treatment taken on top of the standard blood pressure lowering medications.
Seven hundred and thirty (730) patients with so-called “difficult to lower blood pressure” (resistant hypertension) took part in this study. To participate in the study, it was necessary for patients to switch their blood pressure medications to a standard blood pressure lowering medication. This standard blood pressure lowering medication (a single pill containing 3 anti-hypertensive medications) was taken daily in addition to the study medication.
Most of the patients in the study were over 65 years and were already receiving medication for several other conditions such as diabetes, heart, and kidney disease. Almost 70% of participants had a high body weight (with of BMI greater than or equal to 30 kg/m2).
The addition of aprocitentan to the standard blood pressure lowering medication helped lower blood pressure after 4 weeks of treatment. Aprocitentan reduced blood pressure more than placebo. The changes compared to placebo were likely to reduce the risk of heart and brain damage (this is called a clinically relevant reduction). The reduction of blood pressure was seen with all blood pressure measuring methodologies used in this study such as office and ambulatory blood pressure measurements over 24 hours. After 4 weeks of treatment with aprocitentan, the reduction in both the systolic and diastolic blood pressure ranged from 4 to 7 mmHg.
After the first 4 weeks, all patients were given aprocitentan and the blood pressure lowering effect of aprocitentan continued for 48 weeks until the end of the study. This was verified by changing half of the patients to placebo at Week 36. The blood pressure lowering effect remained in patients who continued with aprocitentan for the last 12 weeks but was lost for the patients who received placebo. The difference in systolic blood pressure between these 2 groups of patients was from 6 to 9 mmHg. The diastolic blood pressure difference between the 2 groups was 5 to 8 mmHg.
Aprocitentan was safe and well tolerated during long-term treatment (up to 48 weeks). Only a small number of patients stopped aprocitentan during the study. The main side effect (adverse event) was oedema (swelling in arms, legs, or ankles because of fluid/water accumulation). 7 patients stopped aprocitentan during the 48 weeks duration of the study because of this side effect. For further information on side effects observed during this study, please refer to the record on ClinicalTrials.gov (NCT03541174).REC name
Scotland B REC
REC reference
18/SS/0079
Date of REC Opinion
7 Aug 2018
REC opinion
Further Information Favourable Opinion