What is the mechanism of action of this treatment?

The most common treatments for Pulmonary Arterial Hypertension (PAH) include phosphodiesterase-5 inhibitors (PDE5Is) like sildenafil and tadalafil, endothelin receptor antagonists (ERAs) such as bosentan and ambrisentan, and prostacyclin analogs like epoprostenol and treprostinil. PDE5Is work by inhibiting the enzyme phosphodiesterase-5, leading to increased levels of cyclic GMP, which causes vasodilation and reduces pulmonary arterial pressure. ERAs block the effects of endothelin-1, a potent vasoconstrictor, thereby promoting vasodilation and reducing vascular resistance. Prostacyclin analogs mimic the effects of prostacyclin, a natural vasodilator, and inhibit platelet aggregation, leading to improved blood flow and reduced pressure in the pulmonary arteries. These mechanisms are crucial for PAH patients as they help alleviate symptoms, improve exercise capacity, and potentially slow disease progression.

What side effects are associated with this type of intervention?

Common treatments for Pulmonary Arterial Hypertension (PAH) include endothelin receptor antagonists (ERAs) like bosentan and ambrisentan, phosphodiesterase-5 inhibitors (PDE5Is) such as sildenafil and tadalafil, and prostacyclin analogues like epoprostenol and treprostinil. Known side effects of ERAs include liver enzyme elevation, headache, and peripheral edema. PDE5Is can cause headaches, flushing, dyspepsia, and visual disturbances. Prostacyclin analogues often lead to jaw pain, nausea, diarrhea, and flushing. These side effects are important considerations when managing PAH treatment.

What other types of research exist?

Promising novel alternatives to RT234 for PAH treatment in 2024 include: 1) Inhaled fasudil, a Rho-kinase inhibitor, which has shown acute vasodilator effects. 2) Oral combination therapies involving PDE5Is like sildenafil or tadalafil, which improve exercise capacity and hemodynamics. 3) Endothelin receptor antagonists such as macitentan, which target endothelin receptors to reduce vasoconstriction. 4) Inhaled prostanoids like iloprost and treprostinil, which have demonstrated improvements in exercise capacity and functional class.

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Phosphodiesterase-5 (PDE-5) Inhibitor

Inhaled Vardenafil for Pulmonary Arterial Hypertension (VIPAH-PRN 2B Trial)

Q: What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Pulmonary Arterial Hypertension (PAH) that function as vasodilators or agents to reduce pulmonary arterial pressure. These include phosphodiesterase-5 inhibitors (PDE5Is) like sildenafil and tadalafil, endothelin receptor antagonists (ERAs) such as bosentan and ambrisentan, and soluble guanylate cyclase stimulators like riociguat. Additionally, prostacyclin analogues such as epoprostenol, treprostinil, and iloprost have been approved. These medications aim to improve pulmonary hemodynamics and exercise capacity, aligning with the goals of the RT234 trial.

Phase 2

Recruiting

Research Sponsored by Respira Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must have had a ventilation/perfusion (V/Q) scan, computerized tomography angiogram, or pulmonary arteriogram that rules out chronic thromboembolic pulmonary hypertension (CTEPH).

Ages 18 and 80 years, inclusive.

Must not have

Use of PAH medications that are not taken by mouth.

Portopulmonary hypertension, portal hypertension, or chronic liver disease determined to be Child-Pugh B or C, including hepatitis B virus and/or hepatitis C virus (HCV).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline cpet to post-treatment cpet at 7 to 14 days following baseline cpet

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing an inhaled medication called RT234. It aims to help people with pulmonary arterial hypertension (PAH) breathe better and exercise more easily. The medication works by widening the blood vessels in the lungs, making it easier for the heart to pump blood. RT234 is being developed to improve exercise tolerance and symptoms in patients with PAH.

Who is the study for?

Adults aged 18-80 with a confirmed diagnosis of WHO Group 1 Pulmonary Arterial Hypertension (PAH) who can walk at least 150 meters and are on stable PAH medication may qualify. Exclusions include vision loss from optic neuropathy, use of non-oral PAH meds, recent pulmonary rehab, sudden hearing loss, Down syndrome, severe blood or heart conditions, liver disease, uncontrolled asthma or hypertension, certain infections in HIV patients.

What is being tested?

The trial is testing RT234 - vardenafil inhalation powder delivered via an Axially Oscillating Sphere dry powder inhaler to see if it improves exercise ability in PAH patients. Participants will undergo a Cardiopulmonary Exercise Test (CPET) to measure the drug's effects.

What are the potential side effects?

While not explicitly listed for this trial summary request, common side effects for similar treatments could include coughing or throat irritation due to inhaling the powder; headaches; dizziness; upset stomach; and potential risks associated with changes in blood pressure.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I've had a scan that shows I don't have CTEPH.

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I am between 18 and 80 years old.

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I have had a right heart catheterization confirming pulmonary arterial hypertension.

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I can walk at least 150 meters without stopping.

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I experience moderate to severe symptoms affecting my daily activities.

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I am on up to 3 oral or inhaled treatments for PAH and my condition is stable.

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My pulmonary arterial hypertension is confirmed by a right heart catheterization.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am using non-oral medication for pulmonary arterial hypertension.

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I have severe liver disease or hypertension related to liver problems.

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I have irregular heartbeats that are sudden or not well-controlled.

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I have a history of fainting or sudden drops in blood pressure.

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I have a history of heart disease affecting the left side of my heart.

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I have experienced sudden hearing loss.

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I have a long-term asthma condition that is not well-controlled.

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My heart's electrical activity, measured by ECG, is within normal limits.

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I have vision loss due to a specific type of optic nerve damage.

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I have had a procedure to create a hole in the wall between the upper chambers of my heart.

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I have severe kidney problems or need dialysis.

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My high blood pressure is not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline cpet to post-treatment cpet at 7 to 14 days following baseline cpet

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline cpet to post-treatment cpet at 7 to 14 days following baseline cpet

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline cpet to post-treatment cpet at 7 to 14 days following baseline cpet for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Vital Signs

Change in peak oxygen consumption (VO2) assessed by CPET after RT234 dosing

Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)

Secondary study objectives

Change in 6-minute walk distance (6MWD)

Change in perceived dyspnea

Other study objectives

Change in Duke Activity Status Index (DASI)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: RT234 2.0 mg Cohort 3Experimental Treatment1 Intervention

RT234 at a capsule dose strength of 2.0 mg.

Group II: RT234 1.0 mg Cohort 2Experimental Treatment1 Intervention

RT234 at a capsule dose strength of 1.0 mg.

Group III: RT234 0.5 mg Cohort 1Experimental Treatment1 Intervention

RT234 at a capsule dose strength of 0.5 mg.

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Pulmonary Arterial Hypertension (PAH) include phosphodiesterase-5 inhibitors (PDE5Is) like sildenafil and tadalafil, endothelin receptor antagonists (ERAs) such as bosentan and ambrisentan, and prostacyclin analogs like epoprostenol and treprostinil. PDE5Is work by inhibiting the enzyme phosphodiesterase-5, leading to increased levels of cyclic GMP, which causes vasodilation and reduces pulmonary arterial pressure. ERAs block the effects of endothelin-1, a potent vasoconstrictor, thereby promoting vasodilation and reducing vascular resistance. Prostacyclin analogs mimic the effects of prostacyclin, a natural vasodilator, and inhibit platelet aggregation, leading to improved blood flow and reduced pressure in the pulmonary arteries. These mechanisms are crucial for PAH patients as they help alleviate symptoms, improve exercise capacity, and potentially slow disease progression.

Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis.Key articles and guidelines in the management of pulmonary arterial hypertension: 2011 update.