Inhaled Treprostinil for Pulmonary Hypertension

Overseen By Colleen Irlbeck

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Disqualifiers: Pregnancy, Inability to exercise, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an inhaled medication called treprostinil to determine its effects on individuals with pulmonary arterial hypertension related to interstitial lung disease (PAH-ILD). Researchers aim to discover if treprostinil can help these individuals exercise more easily and improve their quality of life after three months of use. The trial includes two groups: individuals with PAH-ILD who will receive the medication, and healthy volunteers who will assist researchers in understanding the exercise process. This trial may suit those diagnosed with PAH-ILD who struggle with exercise due to their condition. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that inhaled treprostinil is likely to be safe for humans?

Previous studies have shown that inhaled treprostinil is safe and generally well-tolerated by patients. Research indicates that patients with pulmonary hypertension using inhaled treprostinil improved their exercise capacity and lung function. While side effects occurred, they were manageable and not severe. Specifically, one study found that even at higher doses, patients still tolerated inhaled treprostinil well. Another study showed fewer cases of patients worsening with this treatment compared to those taking a placebo (a dummy treatment with no active drug). Overall, these studies suggest that the safety of inhaled treprostinil is favorable. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for pulmonary hypertension?

Inhaled treprostinil is unique because it offers a new delivery method for treating pulmonary hypertension, specifically in patients with PAH-ILD (Pulmonary Arterial Hypertension associated with Interstitial Lung Disease). Most treatments for pulmonary hypertension, like oral or intravenous medications, can have systemic side effects and may require invasive administration methods. However, inhaled treprostinil directly targets the lungs, potentially improving the efficacy and reducing side effects by delivering the medication right where it's needed. Researchers are excited about this approach because it could lead to better outcomes and a higher quality of life for patients by simplifying the treatment process and enhancing the drug's effectiveness.

What evidence suggests that inhaled treprostinil might be an effective treatment for pulmonary hypertension?

Research has shown that inhaled treprostinil can help people with pulmonary hypertension caused by interstitial lung disease (ILD) exercise more effectively. One study found that patients using inhaled treprostinil walked farther in a six-minute walk test than those who did not use it. Another study found that inhaled treprostinil reduced the risk of disease progression by 39% compared to a placebo. The INCREASE trial demonstrated that this treatment improves exercise ability and reduces the chance of disease worsening. In this trial, patients diagnosed with PAH-ILD received inhaled treprostinil and underwent specific assessments, highlighting its potential effectiveness for pulmonary hypertension related to ILD. ^{4 5 6 7 8}

Who Is on the Research Team?

Yogesh N Reddy, M.B.B.S

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults over 18 with suspected PAH-ILD undergoing right heart catheterization, and healthy volunteers without lung disease or pulmonary hypertension. It's not for anyone under 18.

Inclusion Criteria

Undergoing cardiac catheterization for clinical indications at Mayo Clinic Rochester over a 12-month period.

I am suspected to have high blood pressure in the lungs due to lung disease and will undergo a heart procedure.

I am healthy with no lung, heart, muscle diseases or high blood pressure in the lungs.

Exclusion Criteria

I am under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled treprostinil and undergo RHC while exercising

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Treprostinil

Trial Overview The study is testing the drug treprostinil inhaled by patients with PAH-ILD to see how it affects their ability to exercise and quality of life after three months. Some may undergo optional muscle biopsies or RHC while exercising.

How Is the Trial Designed?

Group I: PAH-ILD Patients Experimental Treatment 3 Interventions

Patients diagnosed with PAH-ILD will undergo RHC while exercising, receive inhaled treprostinil, and undergo an optional muscle biopsy.

Group II: Healthy Volunteers Experimental Treatment 2 Interventions

Healthy volunteers will undergo RHC while exercising and an optional muscle biopsy.

Treprostinil is already approved in United States, European Union for the following indications:

Approved in United States as Remodulin for:

• Pulmonary Arterial Hypertension

Approved in European Union as Remodulin for:

• Pulmonary Arterial Hypertension

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

United Therapeutics

Industry Sponsor

Trials

112

Recruited

14,500+

Dr. Martine Rothblatt

United Therapeutics

Chief Executive Officer since 1996

PhD in Medical Ethics from the Royal London College of Medicine and Dentistry, JD and MBA from UCLA

Dr. Michael Benkowitz

United Therapeutics

Chief Medical Officer since 2023

MD from Harvard Medical School

Published Research Related to This Trial

Treprostinil (Remodulin) is a new treatment option for pulmonary hypertension, highlighting its potential as an effective therapy for this condition.

The study outlines a comprehensive multidisciplinary management plan that includes a flow chart to address high-risk issues associated with the use of treprostinil, emphasizing the importance of safety in its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient safety challenges in treprostinil therapy. Roncesvalles, A., Lee, FW., Camamo, J., et al.[2017]

In a study of 57 men undergoing TUR-P or TUI-P, both solifenacin and mirabegron effectively reduced overactive bladder (OAB) symptoms at 2 weeks post-surgery, indicating their efficacy in managing immediate post-operative OAB symptoms.

Mirabegron demonstrated a better safety profile compared to solifenacin, as two patients in the solifenacin group experienced urinary retention, suggesting that β-3 agonists may be a safer option for patients after prostate surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating overactive bladder symptoms after transurethral prostatic surgery for benign prostatic hyperplasia - Which medication to choose? Lee, CL., Kuo, HC.[2023]

Tyvaso DPI is a portable, breath-powered inhaler that delivers treprostinil for treating pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease, offering a passive administration method that enhances patient compliance.

In clinical studies, Tyvaso DPI demonstrated similar drug exposure and safety profiles to nebulized treprostinil, with a low incidence of adverse events and high patient satisfaction, making it a suitable option for patients seeking a convenient and effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyvaso DPI: Drug-device characteristics and patient clinical considerations. McEvoy, C., Argula, R., Sahay, S., et al.[2023]

LIQ861, a dry-powder formulation of treprostinil, shows comparable bioavailability to the nebulized Tyvaso® inhalation solution, with exposure parameters indicating similar effectiveness in delivering the medication to patients with pulmonary arterial hypertension (PAH).

Both LIQ861 and Tyvaso® were well tolerated by participants, suggesting that LIQ861 offers a safe and convenient alternative for PAH patients, allowing for effective treatment in just 1 to 2 breaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative bioavailability of inhaled treprostinil administered as LIQ861 and Tyvaso® in healthy subjects. Roscigno, RF., Vaughn, T., Parsley, E., et al.[2021]

Treprostinil is an effective treatment for pulmonary arterial hypertension (PAH) and is available in three formulations: intravenous/subcutaneous (Remodulin®), inhaled (Tyvaso®), and oral (Orenitram®).

Pharmacokinetic studies in both healthy volunteers and PAH patients provide important insights that can help clinicians make informed decisions about the most suitable route of administration for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Review of Treprostinil Pharmacokinetics via Four Routes of Administration. Kumar, P., Thudium, E., Laliberte, K., et al.[2018]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2008470

Inhaled Treprostinil in Pulmonary Hypertension Due to ... In patients with pulmonary hypertension due to interstitial lung disease, inhaled treprostinil improved exercise capacity from baseline.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9450844/

Real‐world use of inhaled treprostinil for lung disease ... The effect of inhaled treprostinil on 6MWD also drove a reduction in clinical worsening risk by 39% (95% CI: 0.40–0.92; p = 0.04) compared to placebo‐treated ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2212534524001217

Efficacy, safety, and pharmacokinetics of inhaled ... The INCREASE trial demonstrated that inhaled treprostinil can improve exercise capacity and decrease clinical worsening without any significant safety issues.

4. atsjournals.org atsjournals.org/doi/10.1164/rccm.202107-1766OC

Efficacy of Inhaled Treprostinil on Multiple Disease ... Patients who received inhaled treprostinil were significantly less likely to experience further disease progression events after an initial event compared with ...

5. publications.ersnet.org publications.ersnet.org/content/erj/61/6/2300944

Inhaled treprostinil for interstitial lung disease-associated ... The results of the ongoing TETON studies are eagerly awaited regarding the potential effectiveness of inhaled treprostinil to treat IPF and potentially ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4824653/

Safety and Tolerability of High-dose Inhaled Treprostinil in ... In conclusion, iTRE appears to be safe and generally well-tolerated at doses > 9 breaths four times daily among PH patients in our single center experience.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00741819

NCT00741819 | Safety Evaluation of Inhaled Treprostinil ... Overall safety of transitioning from inhaled iloprost to inhaled treprostinil was assessed by type and frequency of adverse events. up to 24 months. Secondary ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35514770/

BREEZE: Open-label clinical study to evaluate the safety ... These results demonstrate that, in patients with PAH, transition from treprostinil inhalation solution to TreT is safe, well-tolerated, and accompanied by ...