CLINICAL TRIALS PROFILE FOR MACITENTAN; TADALAFIL

All Clinical Trials for macitentan; tadalafil

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02558231 ↗	The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension	Completed	Actelion	Phase 3	2016-05-01	The objective of this clinical trial is to compare the efficacy and safety of an initial triple oral treatment regimen (macitentan, tadalafil, selexipag) versus an initial dual oral treatment regimen (macitentan, tadalafil, placebo) in newly diagnosed, treatment-naïve patients with pulmonary arterial hypertension.
NCT02968901 ↗	Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)	Terminated	Actelion	Phase 4	2015-09-01	The purpose of the study is to document the effect of first line dual oral combination therapy with macitentan 10mg and tadalafil 40mg on pulmonary vascular resistance (PVR) in treatment-naïve patients with newly diagnosed pulmonary arterial hypertension (PAH).
NCT03215966 ↗	A Study to Compare the Macitentan-tadalafil Fixed Dose Combination Tablet Relative to the Concomitant Administration of the Reference Tablets of Macitentan and Tadalafil in Healthy Subjects	Completed	Actelion	Phase 1	2017-08-07	The primary objective of this study is to demonstrate that macitentan and tadalafil administered as a fixed combination is bioequivalent to both compounds given as separate tablets given at the same doses as in the fixed combination (i.e. whether the amounts of macitentan and tadalfil which reach the blood are comparable).
NCT03904693 ↗	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)	Recruiting	Almac Clinical Technologies	Phase 3	2019-07-29	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.
NCT03904693 ↗	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)	Recruiting	Covance	Phase 3	2019-07-29	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.
NCT03904693 ↗	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)	Recruiting	Frontier Science Foundation	Phase 3	2019-07-29	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.

Clinical Trial Conditions for macitentan; tadalafil

Condition Name

Condition Name for macitentan; tadalafil
Intervention	Trials
Healthy	4
PAH	2
Pulmonary Arterial Hypertension	2
Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)	1

Condition MeSH

Condition MeSH for macitentan; tadalafil
Intervention	Trials
Familial Primary Pulmonary Hypertension	3
Pulmonary Arterial Hypertension	3
Hypertension	3

Clinical Trial Locations for macitentan; tadalafil

Trials by Country

Trials by Country for macitentan; tadalafil
Location	Trials
United States	38
Canada	7
Germany	3
Belgium	3
Spain	2

Trials by US State

Trials by US State for macitentan; tadalafil
Location	Trials
Arizona	3
California	2
Texas	2
Pennsylvania	2
Ohio	2

Clinical Trial Progress for macitentan; tadalafil

Clinical Trial Phase

Clinical Trial Phase for macitentan; tadalafil
Clinical Trial Phase	Trials
PHASE1	2
Phase 4	1
Phase 3	2

Clinical Trial Status

Clinical Trial Status for macitentan; tadalafil
Clinical Trial Phase	Trials
Completed	7
Recruiting	2
Terminated	1

Clinical Trial Sponsors for macitentan; tadalafil

Sponsor Name

Sponsor Name for macitentan; tadalafil
Sponsor	Trials
Actelion	6
Janssen Research & Development, LLC	2
Humanis Saglık Anonim Sirketi	2

Sponsor Type

Sponsor Type for macitentan; tadalafil
Sponsor	Trials
Industry	11
Other	3

Last updated: July 28, 2026

Macitentan and Tadalafil: Clinical Trials Update, Market Analysis, and Revenue Projections for Combination Use in Pulmonary Arterial Hypertension

What is the current clinical trial landscape for macitentan and tadalafil in pulmonary arterial hypertension?

Fast answer: The active clinical narrative for macitentan + tadalafil sits in pulmonary arterial hypertension (PAH) where both agents target nitric oxide–sGC–cGMP signaling (tadalafil) and endothelin receptor antagonism (macitentan). As of the current public record used for this update set, no globally dominant Phase 3 “combo adjudication” program with a single filing-ready pivotal endpoint footprint is identified for the macitentan + tadalafil pairing across major registries; the evidence base is primarily derived from (1) established monotherapy and (2) multi-therapy PAH regimens where combination use is standard-of-care and where tadalafil has a PAH label history.

Clinical trial update focus areas

1. Regimen studies in PAH: Trials evaluate additive hemodynamic benefit, WHO functional class improvement, and risk reduction markers across background endothelin receptor antagonists and PDE5 inhibitors.
2. Biomarker and functional endpoints: 6-minute walk distance (6MWD), pulmonary vascular resistance (PVR), NT-proBNP, and time-to-clinical-worsening endpoints.
3. Subpopulations: Treatment-naïve, background therapy, and regimen escalation studies.

Key checkpoint endpoints used in PAH combo trials

• Time to clinical worsening or death
• Change from baseline in 6MWD
• Change in PVR (invasive hemodynamics)
• Change in WHO functional class
• NT-proBNP dynamics

Interpretation for business planning

• Combination strategy R&D risk is lower if the objective is “add-on incremental benefit” rather than a standalone pivotal combo proof.
• Pivotal-path acceleration depends on whether an existing PAH combo protocol already defines a risk-based composite endpoint and can support label expansion in a defined “background therapy” setting.

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Which clinical trials are testing macitentan plus tadalafil, and what endpoints are they using?

Fast answer: Public clinical trial visibility for this specific pairing is generally fragmented across registries and protocol arms where tadalafil is used as part of broader PAH background therapy. The most investable thesis is that PAH trial designs already accept PDE5 inhibitor + endothelin pathway combinations; the question for future combo studies is whether they will generate label-impacting differentiation versus class-standard add-on therapy.

Endpoint map for combination evaluation

• Primary hemodynamic endpoints: PVR, mean pulmonary arterial pressure (mPAP), cardiac index
• Functional endpoints: 6MWD, WHO functional class change
• Clinical endpoints: clinical worsening (hospitalization, PAH progression), death
• Safety monitoring: hypotension risk signal (tadalafil), edema/headache, liver enzyme monitoring (macitentan), anemia surveillance (endothelin receptor antagonist class signal)

Common operational design features

• Background PAH therapy stratification
• Dose optimization periods
• Event-driven designs for time-to-worsening programs
• Echo and catheterization schedule milestones

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How does macitentan compare with other PAH background agents when paired with tadalafil?

Fast answer: In PAH treatment algorithms, macitentan is the endothelin receptor antagonist most commonly paired with PDE5 inhibitors due to its established role and event-reduction evidence in PAH monotherapy programs. Compared with other background ET receptor antagonists, the business question is less “mechanism” and more “payer-relevant outcome signal plus tolerability profile” that sustains durable combination prescribing.

Comparative regimen logic

• Endothelin receptor blockade + PDE5 inhibition reduces complementary vasoconstrictor pathways
• The combination is used across risk categories, with escalation guided by 6MWD, NT-proBNP, hemodynamics, and WHO class
• Choosing macitentan as background affects:
  • tolerability management in long-term use
  • adherence patterns driven by side-effect burden (fluid retention, anemia monitoring)
  • access dynamics given payer preference and contracting

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What is the commercial market opportunity for macitentan and tadalafil in PAH combination therapy?

Fast answer: The market opportunity is driven by (1) the PAH patient pool and diagnosis expansion, (2) uptake of combination therapy as risk-based standard-of-care, and (3) payer preference for established outcome-proven agents. The combination’s commercial ceiling depends on how effectively it captures:

• newly diagnosed high-risk patients needing rapid escalation
• patients failing monotherapy where dual oral therapy is the next step
• add-on therapy in long-term maintenance

Market sizing mechanics used for projections (framework)

• Treatable PAH prevalence and incident base
• Proportion receiving dual oral therapy vs triple therapy vs parenteral approaches
• Share-of-therapy within dual oral regimens (ETRA-based + PDE5 inhibitor-based)
• Persistence and discontinuation rates
• Pricing and net-to-gross after rebates and contracting

Commercial demand drivers

• Oral regimen preference vs parenteral prostacyclin strategies
• Guideline-aligned escalation pathways
• Payer tendency to cover established agents earlier in therapy lines to prevent costly hospitalizations

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When do macitentan and tadalafil face exclusivity and patent expiration pressure?

Fast answer: A precise exclusivity and patent timeline requires a jurisdiction- and product-specific Orange Book / regulatory dossier mapping. This response does not provide a verified expiration schedule because no jurisdictional patent list is included in the input set.

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What is the Orange Book status of macitentan and tadalafil, and how does it affect generic entry risk?

Fast answer: This requires Orange Book listing verification for the specific dosage forms and strengths for each product. No Orange Book listing dataset is included in the provided material set, so a non-fabricated status readout cannot be produced here.

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How many patents protect macitentan and tadalafil combination use, and where are the likely litigation hotspots?

Fast answer: Patent coverage for combination use splits across product composition-of-matter, formulation, manufacturing, and method-of-use. Without an enumerated patent list tied to the exact product labels and filings, a verified “number of patents” and litigation hotspots cannot be provided without risking inaccuracies.

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What patent litigation or Paragraph IV challenges could impact macitentan and tadalafil market projections?

Fast answer: Litigation and Paragraph IV challenges must be tied to verified dockets (FDA Orange Book triggers plus court filings). No validated case list is included in the provided inputs, so no reliable litigation impact forecast is possible in this response.

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What are the highest-value formulation and method-of-use IP risks for any next-gen macitentan or tadalafil product?

Fast answer: For PAH oral therapies, typical high-value IP buckets include:

• fixed-dose vs co-pack combinations (if any)
• extended-release reformulations
• polymorphs and solid-state forms
• improved dissolution profiles
• manufacturing process controls that improve stability
• method-of-use claims linked to risk stratification or background therapy combinations

A verified mapping to active patents requires explicit patent enumeration tied to current product labels.

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Which companies are positioned to capture PAH combo therapy share using macitentan and tadalafil?

Fast answer: This depends on:

• brand status and contracting strength for both drugs
• channel access and distribution coverage
• ability to meet payer requirements for PAH step therapy

A precise company-share landscape requires a verified commercial dataset and payer coverage inputs not present in the provided material set.

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How does the macitentan + tadalafil commercial outlook change under a triple-therapy vs dual-therapy guideline scenario?

Fast answer: Dual oral therapy competes with up-front or rapid triple combination use (ETRA + PDE5 inhibitor + prostacyclin-pathway therapy) and with earlier parenteral prostacyclin for certain risk profiles. Macitentan + tadalafil share can compress if:

• guidelines favor earlier triple therapy initiation
• payers require higher “risk proof” for dual oral coverage
• new agents shift standard-of-care sequencing

Conversely, share can expand if:

• dual oral therapy becomes the default escalation step for intermediate-risk patients
• cost-effectiveness pressure shifts prescribing toward oral combinations
• tolerability improves and supports persistence

This directional view is deterministic; it is not a numeric projection without market input data.

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Market projection model: what revenue outcomes are most plausible for macitentan and tadalafil combined use?

Fast answer: Quantitative revenue projections require baseline sales, patient coverage rates, utilization, pricing, and competitive dynamics. No numeric sales baselines or payer coverage datasets are included in the provided inputs, so no credible revenue forecast can be generated in this response without fabricating figures.

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Key Takeaways

• The macitentan + tadalafil combination story is anchored in PAH pathway complementarity (endothelin blockade plus PDE5 inhibition) and guideline-aligned dual oral therapy sequencing.
• Trial development visibility for the specific pairing appears fragmented rather than dominated by a single, widely recognizable pivotal Phase 3 combo program in the current public snapshot used for this response.
• Clinical and commercial success hinges on (1) achieving differentiated clinical endpoints that matter to risk-based decision-making and (2) contracting dynamics that determine uptake of dual oral therapy versus early triple therapy.
• A verified exclusivity/patent and Orange Book status timeline cannot be stated here without a validated listing and jurisdictional patent docket dataset.

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FAQs

1. Are macitentan and tadalafil approved together for PAH, and what does the label imply for sequencing?
2. Do trials show improved hemodynamics (PVR or mPAP) with endothelin receptor antagonists plus tadalafil versus monotherapy?
3. What safety monitoring differences exist when combining macitentan with tadalafil in PAH patients?
4. How do payers typically manage coverage between dual oral therapy (macitentan + tadalafil) and triple therapy in PAH?
5. What endpoints (NT-proBNP, 6MWD, clinical worsening) most influence adoption of PAH combination regimens in real-world prescribing?

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References

1. (No citable sources were provided in the input for this update set.)