Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)

Summary

Combination therapy in pulmonary arterial hypertension (PAH) has been the subject of active investigation for more than a decade, with the benefit of targeting different pathways known to be involved in the pathogenesis of the disease. Adherence to prescribed therapy has an impact on clinical outcomes. Reducing the pill/tablet count and frequency has a major impact on patients' adherence to therapies and therefore the observed clinical outcomes. One way to simplify treatment is to use fixed-dose combination (FDC) products that combine multiple treatments targeting different pathways into a single tablet.

This study aims to demonstrate that the FDC of macitentan and tadalafil is more effective than therapy with 10 mg of macitentan alone or 40 mg of tadalafil alone. This phase 3 study will evaluate the efficacy and safety at 16 weeks of an FDC (macitentan 10 mg and tadalafil 40 mg) against these two PAH-approved therapies given as monotherapy to further confirm the added value of the FDC.

Conditions

• Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)

Interventions

DRUG

FDC macitentan/tadalafil

Film-coated tablet with 10 mg macitentan and 40 mg tadalafil, to be administered orally once daily.

DRUG

Macitentan 10 mg

Film-coated tablet with 10 mg macitentan, to be administered orally once daily.

DRUG

Tadalafil 40 mg

Film-coated tablet with 40 mg tadalafil (2 x 20 mg tablets), to be administered orally once daily.

DRUG

Placebo FDC

Matching placebo not containing any active substance but otherwise identical in appearance to the respective active drug tablet, to be administered orally once daily.

DRUG

Placebo macitentan

Matching placebo not containing any active substance but otherwise identical in appearance to the respective active drug tablet, to be administered orally once daily.

DRUG

Placebo tadalafil

Matching placebo not containing any active substance but otherwise identical in appearance to the respective active drug tablet, to be administered orally once daily.

Sponsors & Collaborators

• Actelion

  lead INDUSTRY

Principal Investigators

• Hany Rofael, MD · Janssen, LP

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-07-29

Primary Completion

2022-08-23

Completion

2024-09-27

FDA Drug

Yes

Countries

• United States
• Australia
• Brazil
• Bulgaria
• Canada
• China
• Czechia
• Germany
• Hungary
• Italy
• Japan
• Malaysia
• Mexico
• Poland
• Russia
• South Africa
• Spain
• Taiwan
• Turkey (Türkiye)

Study Locations