Date: 2016-07-06
Type of information: Initiation of the trial
phase: 3
Announcement: initiation of the trial
Company: Actelion (Switzerland)
Product: pediatric formulation of Opsumit® (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. The pediatric formulation is a round dispersible tablet that is neutral in taste. It comes in three different dose strengths (containing 0.5 mg, 2.5 mg and 5.0 mg macitentan). To make them easier for children to swallow, the tablets can be dispersed in water on a teaspoon.
Disease: pulmonary arterial hypertension
Therapeutic area: Rare diseases - Cardiovascular diseases - Autoimmune diseases
Country:
Trial
details: TOMORROW (pediaTric use Of Macitentan tO delay disease pRogRessiOn in PAH Worldwide) is a multicenter, open-label, randomized, event-driven study to assess the efficacy, safety and pharmacokinetics of macitentan versus standard of care in children with pulmonary arterial hypertension. The study will enroll patients with an age range from 1 month to 18 years in more than 20 countries. The patients will be randomized in a 1:1 ratio into two treatment groups - macitentan or standard of care as per local practice. The trial is expected to last up to 6 years, with patients remaining in the study until the target number of primary efficacy endpoints is met. The primary efficacy endpoint is defined as time to the first Clinical Event Committee (CEC) confirmed disease progression event, comprising: Death (all causes), or Atrial septostomy or Pott's anastomosis, or registration on lung transplant list, or Hospitalization due to PAH, or Clinical worsening of PAH
Due to the open-label nature of the study, the management of investigational centers as well as data management, data analysis and coordination of the CEC will be conducted by a CRO. The primary endpoints of the study will be adjudicated by a blinded CEC, in a similar approach to that used in the Phase III SERAPHIN study, where macitentan was studied in adult patients with PAH. An interim analysis for early efficacy or futility is planned when at least 131 CEC-confirmed first disease progression events (70% information fraction) have occurred. If Actelion completes the study as outlined, the company can apply for the extension of the marketing exclusivity for Opsumit both in the US and the European Union.
Latest
news: * On July 6, 2016, Actelion announced that it will be initiating a Phase III study to evaluate the effect of macitentan on delaying disease progression in children with PAH using a pediatric formulation of macitentan (Opsumit®). TOMORROW (pediaTric use Of Macitentan tO delay disease pRogRessiOn in PAH Worldwide) will enroll children between the age of 1 month and 18 years in more than 20 countries. Initially, only children aged between 2 and < 18 years will be enrolled, and pharmacokinetic profiles collected in the study for up to 40 patients will allow Actelion to determine the doses for younger patients. Once the dose is determined, the study protocol will be amended to include children below 2 years of age. The children will be randomized in a 1:1 ratio into two treatment groups - macitentan administered as a pediatric formulation or standard of care as per local practice. The pediatric formulation of macitentan is a round dispersible tablet that is neutral in taste. It is available in three different dose strengths, containing 0.5 mg, 2.5 mg and 5.0 mg macitentan. To make them easier for children to swallow, the tablets can be dispersed in water on a spoon.
The trial is expected to last up to 6 years, with children being enrolled until 187 primary efficiency endpoint events have occurred. The primary efficacy endpoint is defined as the time to the first Clinical Event Committee (CEC) confirmed outcome event.
