Date: 2018-06-20
Type of
information: Treatment of the first patient
phase: 3
Announcement: treatment of the first patient
Company: Idorsia (Switzerland)
Product: aprocitentan
Action
mechanism:
- dual endothelin receptor antagonist. Aprocitentan is an orally active dual endothelin receptor antagonist. Aprocitentan counteracts these deleterious effects in animal models of hypertension, including in salt-sensitive models. In such models, aprocitentan also provide significant blood pressure lowering effects on top of existing therapies (e.g. renin angiotensin system blockers).
- In a dose-finding study to explore the efficacy, safety and tolerability of aprocitentan in 490 patients with essential hypertension, aprocitentan significantly lowered blood pressure in a dose-dependent manner.
- In December 2017, Idorsia entered into a collaboration with Janssen Biotech, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to jointly develop and commercialize aprocitentan and any of its derivative compounds or products.
Disease: resistant hypertension management in adults
Therapeutic
area: Cardiovascular diseases
Country:
Trial
details:
- PRECISION is a multi-center, double-blinded, placebo-controlled, randomized, parallel-group, Phase 3 study to demonstrate the blood pressure lowering effect of aprocitentan when added to standard-of-care in resistant hypertension patients. Idorsia, following consultation with regulatory agencies, has designed an efficient, single Phase 3 study. The study will address both the short-term efficacy of aprocitentan and the durability of its effect on long-term treatment in a placebo-controlled manner.
- Patients with history of resistant hypertension will undergo a thorough screening and run-in period. This will confirm the diagnosis of resistant hypertension by excluding pseudo or apparent resistant hypertension. During the screening period, patient's background anti-hypertensive therapies will be transitioned to a standardized fixed combination of a calcium channel blocker (amlodipine), an angiotensin receptor blocker (valsartan) and a diuretic (hydrochlorothiazide).
- Patients with true resistant hypertension will then be randomized to receive aprocitentan 12.5 mg, 25 mg, or placebo once-daily. The study consists of 3 sequential treatment periods. The first is a double-bind treatment period designed to demonstrate the effect of aprocitentan on blood pressure at Week 4, compared to placebo. Patients then enter a treatment period where they are treated with 25 mg aprocitentan for 32 weeks. This is followed by a double-blind, randomized withdrawal treatment period where patients will remain either on aprocitentan 25 mg or switch to placebo for 12 weeks. The latter treatment period is designed to demonstrate the durability of the blood pressure lowering effect of aprocitentan. Patients will then enter a 30-day safety follow-up period.
- From the initial screened patient population, at least 600 patients will be randomized and at least 300 patients are expected to complete the study. The study will be conducted in approximately 100 sites in around 20 countries.
Latest
news:
- • On June 20, 2018, Idorsia announced that the first patient has been enrolled into PRECISION, a Phase 3 study to investigate the efficacy and safety of aprocitentan for resistant hypertension management in adults. Clinical and preclinical evidence suggest that resistant hypertension may be endothelin-dependent. Indeed, the endothelin system plays an important role in forms of volume and salt-dependent hypertension, a common feature in patients with resistant hypertension. Endothelin-1 is a potent vasoconstrictor and also induces neurohormonal activation, vascular hypertrophy and remodeling, cardiac hypertrophy and fibrosis, and endothelial dysfunction.
Is
general: Yes
