Date: 2016-11-07
Type of
information: Results
phase: 2
Announcement: results
Company: Actelion (Switzerland)
Product: macitentan
Action
mechanism: endothelin receptor antagonist. Macitentan is an oral dual endothelin receptor antagonist. This means that it is expected to block the receptors (type A and B) which endothelin-1 normally attaches to and activates. Endothelin is a naturally occurring substance that is released from lining of the blood vessels. It is present at raised levels in patients with pulmonary arterial hypertension, causing the blood vessels to constrict and the blood vessel walls to thicken. By blocking endothelin receptors , macitentan is expected to stop endothelin from constricting the blood vessels, thereby leading to a decrease in the blood pressure and a reduction of the symptoms of pulmonary arterial hypertension.
Disease: chronic thromboembolic pulmonary hypertension
Therapeutic
area: Rare diseases - Cardiovascular diseases - Respiratory diseases
Country: Austria, Bulgaria, Canada, Chile, Italy, Netherlands, South Africa, USA, Vietnam (MERIT-1) Austria, Bulgaria, Canada, Chile, Czech Republic, Italy, Republic of Korea, Netherlands, South Africa, Switzerland, USA,Vietnam (MERIT-2)
Trial
details:
- MERIT-1 is a study to evaluate if macitentan is efficient, safe and tolerable enough to be used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH). (NCT02021292)
- MERIT-2 is a long-term study to evaluate if macitentan is safe, tolerable and efficient enough to be used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH). (NCT02060721)
Latest
news:
- • On November 7, 2016, Actelion announced that the MERIT study to assess the efficacy, safety and tolerability of macitentan in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH; Pulmonary hypertension group 4) has met its primary endpoint.
- In MERIT, 80 inoperable CTEPH patients were randomized 1:1 to receive either macitentan 10 mg once daily or placebo. After 16 weeks the treatment effect was a significant 16% reduction in pulmonary vascular resistance (PVR) with macitentan compared with placebo (95% CL: -30%, -1%; p=0.04 intention-to-treat (ITT)). The efficacy observed was consistent across all sub-groups, included patients receiving background PH specific therapy at baseline (61%), including PDE-5 inhibitors (59%). Mean PVR decreased from baseline in both macitentan and placebo groups (geometric mean percent ratios of Week 16/baseline 73.0% and 87.2%, respectively).
- The study also showed a significant positive effect of macitentan compared to placebo on exercise capacity. After 24 weeks of treatment, the mean change in 6-minute walk distance (6-MWD) from baseline was an increase of 35 meters (m) in macitentan and 1 m in placebo. The 6-MWD least-squares mean difference at Week 24 was 34.0 meters between macitentan and placebo (95% CL: 2.9, 65.2 m; p=0.03).
- The MERIT safety set comprised 80 patients, who received at least one dose of study treatment, 40 patients in each macitentan and placebo groups. All 40 patients in the macitentan group and 34 patients in the placebo group completed the protocol-defined treatment period of 24 weeks. Macitentan was well tolerated in this patient population and safety was in general consistent with the known safety profile for macitentan from previous clinical studies. The most frequently reported adverse events that occurred with higher frequency on macitentan vs. placebo were peripheral edema (22.5% vs. 10.0%) and events related to anemia (17.5% vs. 2.5%). Hemoglobin decreases were observed in both macitentan and placebo groups and in only one subject in each group hemoglobin values decreased below 100 g/L during the study. Three (7.5%) patients on macitentan experienced a serious adverse event compared with seven (17.5%) patients on placebo. No elevations of liver aminotransferases greater than three times the upper limit of normal were observed in the study. All treatment discontinuations occurred in the placebo group. During the course of the study, there were two deaths reported, both in patients receiving placebo.
- Full data from this study will be made available through scientific disclosure at an upcoming congress and peer-reviewed publication.
Is
general: Yes
