The efficacy and safety of initial triple versus initial dual oral combination therapy in patients with newly diagnosed pulmonary arterial hypertension

• Register: EUCTR
• Last refreshed on: 13 July 2020
• Main ID: EUCTR2015-003438-28-DK
• Date of registration: 30/05/2016
• Prospective Registration: Yes
• Primary sponsor: Actelion Pharmaceuticals Ltd
• Public title: The efficacy and safety of initial triple versus initial dual oral combination therapy in patients with newly diagnosed pulmonary arterial hypertension
• Scientific title: The efficacy and safety of initial triple versus initial dual oral combination therapy in patients with newly diagnosed pulmonary arterial hypertension: A multi-center, double-blind, placebo-controlled, Phase 3b study - TRITON - Macitentan, Tadalafil and Selexipag Study in Patients with PAH
• Date of first enrolment: 17/08/2016
• Target sample size: 238
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003438-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Global Medical Affairs
• Affiliation: Actelion Pharmaceuticals Ltd

• Name: Global Medical Affairs
• Affiliation: Actelion Pharmaceuticals Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Signed informed consent prior to any study-mandated procedure.
- Initial PAH diagnosis < 6 months prior to enrollment.
- RHC performed between Day -28 and Day 1, meeting all the
following criteria:
• Mean pulmonary artery pressure (mPAP) = 25 mmHg.
• Pulmonary artery wedge pressure or left ventricular end-diastolic
pressure = 15 mmHg.
• PVR = 480 dyn•sec/cm5 (= 6 Wood Units).
• Negative vasoreactivity test mandatory in idiopathic, heritable,
and drug/toxin induced PAH (at this or a previous RHC).
- Symptomatic PAH belonging to one of the following subgroups:
• Idiopathic.
• Heritable.
• Drug or toxin induced.
• Associated with one of the following: Connective tissue disease;
HIV infection; Congenital heart disease.
- 6-minute walk distance (6MWD) = 50 m at screening.
- Women of childbearing potential must not be pregnant, must perform
regular pregnancy tests, and use reliable contraception.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 198
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
- Any PAH-specific drug therapy at any time.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary arterial hypertension (PAH)
MedDRA version: 20.0 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Trade Name: Uptravi
Product Name: Selexipag
Product Code: ACT-293987
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Selexipag
Current Sponsor code: ACT-293987
Other descriptive name: SELEXIPAG
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Opsumit
Product Name: Macitentan
Product Code: ACT-064992
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Macitentan
Current Sponsor code: ACT-064992
Other descriptive name: MACITENTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Adcirca
Product Name: Adcirca
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TADALAFIL
Other descriptive name: TADALAFIL
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: To compare an initial triple oral regimen (macitentan, tadalafil,
selexipag) with an initial dual oral regimen (macitentan, tadalafil,
placebo) in newly diagnosed, treatment-naïve subjects with PAH, with
respect to cardio-pulmonary hemodynamics (other than PVR), exercise
capacity, disease severity, morbidity/mortality, safety, and tolerability.

Timepoint(s) of evaluation of this end point: Baseline to Week 26

Main Objective: To compare the effect on pulmonary vascular resistance (PVR) of an
initial triple oral regimen (macitentan, tadalafil, selexipag) versus an
initial dual oral regimen (macitentan, tadalafil, placebo) in newly
diagnosed, treatment-naïve subjects with pulmonary arterial
hypertension (PAH).

Primary end point(s): Pulmonary vascular resistance

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline to Week 26. For time to the first disease progression event,
baseline to 26 weeks after last patient enrolled.

Secondary end point(s): N-terminal pro B-type natriuretic peptide (NT-proBNP), 6-minute walk
distance, WHO Functional Class, cardiac hemodynamics as assessed by
right heart catheterization, time from randomization to the first disease
progression event

Secondary ID(s)

AC-065A308

2015-003438-28-DE

Source(s) of Monetary Support

Actelion Pharmaceuticals Ltd

Ethics review

Status: Approved
Approval date: 17/08/2016
Contact: