Inhaled Treprostinil for Pulmonary Fibrosis

Recruiting at 160 trial locations

Overseen By Debabrata Bandyopadhyay, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: United Therapeutics

Must be taking: Nintedanib, Pirfenidone

Must not be taking: Prostacyclin, Endothelin antagonists

Disqualifiers: Pregnancy, IPF, Uncontrolled cardiac disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 6

Duration: 52 weeks

698 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of inhaled treprostinil for people with progressive pulmonary fibrosis (PPF), a condition where lung tissue becomes scarred over time, making breathing difficult. Participants will receive either the experimental drug or a placebo through an ultrasonic nebulizer, which converts the medication into a mist for inhalation. The trial seeks individuals diagnosed with PPF who experience worsening symptoms despite standard treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial does not require you to stop your current medications. If you are on nintedanib or pirfenidone, you should continue them if you have been taking them for at least 90 days. If you are on immunosuppressive agents, you should have been on them for at least 120 days before starting the trial.

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

Research has shown that inhaled treprostinil is generally safe for people. Studies have found it to be well-tolerated, even by those with other health conditions. This medication has been used for conditions like pulmonary arterial hypertension (high blood pressure in the lungs) and has shown benefits with manageable side effects.

Previous studies report that some people may experience side effects like coughing or throat irritation, but these are usually mild to moderate. Evidence also supports its safety for patients with interstitial lung disease (a group of lung disorders).

Overall, inhaled treprostinil has been studied extensively, and its safety is well understood. The FDA has approved it for other lung conditions, which supports its use in treating pulmonary fibrosis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary fibrosis?

Unlike the standard treatments for pulmonary fibrosis, which often focus on reducing inflammation or slowing disease progression, inhaled Treprostinil offers a unique approach by directly targeting the blood vessels in the lungs to improve blood flow and oxygenation. This treatment is delivered via an ultrasonic nebulizer, making it easy to administer through inhalation. Researchers are excited because this method might enhance pulmonary function more effectively and quickly than oral or intravenous options and could potentially improve the quality of life for patients with pulmonary fibrosis.

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

Research has shown that inhaled treprostinil, which participants in this trial may receive, can improve symptoms in people with lung conditions like pulmonary fibrosis. One study found that patients could walk farther in six minutes after just four weeks of treatment, with even more improvement by twelve weeks. This treatment is also safe and effective for individuals with other health issues. Inhaled treprostinil has benefited patients with lung and blood vessel problems. Overall, evidence suggests that inhaled treprostinil can enhance lung function in people with pulmonary fibrosis. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Adults diagnosed with progressive pulmonary fibrosis, who are not pregnant or breastfeeding, can join this trial. They must use contraception if applicable and have been on certain treatments for at least 120 days. People with recent lung infections, high oxygen needs, a specific type of lung scarring called IPF, or those using certain PAH therapies recently cannot participate.

Inclusion Criteria

My lung scans show more than 10% fibrosis.

I will use a condom during treatment and for 48 hours after stopping the study drug.

I am not taking nintedanib and pirfenidone at the same time.

Exclusion Criteria

I have severe lung obstruction or more damage from emphysema than scarring on a lung scan.

I haven't taken part in any medical trials involving treatments in the last 30 days.

I have taken medication for pulmonary arterial hypertension in the last 60 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled treprostinil or placebo for 52 weeks, with dose titration as tolerated

52 weeks

6 visits (in-person) at Weeks 4, 8, 16, 28, 40, and 52

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term after completing the main study

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled Treprostinil

Trial Overview The study is testing the safety and effectiveness of inhaled treprostinil delivered via an ultrasonic nebulizer compared to a placebo over one year. It aims to see if this treatment can help people with worsening lung scarring despite standard care.

How Is the Trial Designed?

Group I: Inhaled Treprostinil Experimental Treatment 2 Interventions

Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. Inhaled QID and titrated up to a target of 12 breaths QID or until the subject reaches their maximum clinically tolerated dose.

Group II: Placebo Placebo Group 2 Interventions

Matching placebo inhaled using an ultrasonic nebulizer QID

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

Approved in United States as Tyvaso for:

• Pulmonary arterial hypertension (PAH)
• Pulmonary hypertension associated with interstitial lung disease (PH-ILD)

Approved in European Union as Tyvaso for:

• Pulmonary arterial hypertension (PAH)
• Pulmonary hypertension associated with interstitial lung disease (PH-ILD)

Who Is Running the Clinical Trial?

United Therapeutics

Lead 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

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]

In a pilot study of 40 men who experienced incontinence after robot-assisted radical prostatectomy, the muscarinic receptor antagonist solifenacin was found to be well tolerated, with a 15% withdrawal rate due to side effects.

After 3 months of treatment, 53.8% of participants achieved continence (defined as using zero pads), suggesting potential efficacy, although it remains unclear if the improvement was directly due to the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial of Vesicare™ (solifenacin) in the treatment of urinary incontinence after radical prostatectomy. Liss, MA., Morales, B., Skarecky, D., et al.[2018]

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]

Propiverine hydrochloride is effective in treating detrusor hyperreflexia and overactive bladder symptoms in adults, children, and the elderly, as shown in controlled clinical trials.

It is well tolerated compared to other treatments like oxybutynin, with a lower incidence of side effects such as dry mouth, and has demonstrated long-term safety in studies involving thousands of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, tolerability and safety profile of propiverine in the treatment of the overactive bladder (non-neurogenic and neurogenic). Madersbacher, H., Mürtz, G.[2019]

Inhaled treprostinil (Tyvaso) is a safe and effective treatment for pulmonary arterial hypertension (PAH), with a large study involving 1,333 patients showing it can be well tolerated in routine clinical care.

While patients treated with inhaled treprostinil reported a higher incidence of respiratory-related adverse events, such as cough and throat irritation, these events were consistent with the known safety profile of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An observational study of inhaled-treprostinil respiratory-related safety in patients with pulmonary arterial hypertension. Zamanian, RT., Levine, DJ., Bourge, RC., et al.[2022]

In a study of 94 patients with obstructive urination due to benign prostatic hyperplasia, the combination of finasteride and terazosin led to a significant reduction in prostate size by an average of 17% in 72% of patients over an average follow-up of 16.1 months.

Patients experienced a 55% increase in maximal urine flow rate, indicating improved urination, and the treatment was well tolerated, making it an effective conservative therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A trial of the use of finasteride and terazosin in patients with benign prostatic hyperplasia]. Pushkar', DIu., Kosko, DV., Loran, OB., et al.[2013]

Racemic oxybutynin and its metabolites, particularly R- and S-desethyloxybutynin, exhibit strong antimuscarinic activity, which is important for treating urinary incontinence, as shown in experiments with isolated guinea pig bladder strips.

The study suggests that S-oxybutynin could be developed as a single-enantiomer drug, potentially offering similar therapeutic benefits to oxybutynin with fewer side effects, making it a promising alternative for managing urinary incontinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the antimuscarinic and antispasmodic actions of racemic oxybutynin and desethyloxybutynin and their enantiomers with those of racemic terodiline. Smith, ER., Wright, SE., Aberg, G., et al.[2017]

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]

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]

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]

Citations

1. tyvasohcp.com tyvasohcp.com/ph-ild/efficacy-safety/efficacy/

TYVASO® INCREASE Study Efficacy Patients who took TYVASO saw improvement in 6MWD starting as early as week 4 and reached statistical significance by week 12.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12224286/

Practical Considerations for Managing Patients on Tyvaso ... While comorbidities should be considered, inhaled treprostinil remains safe and effective even in these patients [33, 34]. A recently published ...

3. ir.unither.com ir.unither.com/press-releases/2025/09-02-2025-120037033

United Therapeutics Corporation Announces TETON-2 ... Results of the successful phase 3 TETON-2 study of inhaled treprostinil in idiopathic pulmonary fibrosis will be presented in an oral ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1094553923000780

Tyvaso DPI: Drug-device characteristics and patient clinical ... Inhaled treprostinil results in clinical improvements in patients with PAH and PH-ILD, as well as hemodynamic improvement in patients with PAH [21,[25], [26], [ ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/214324Orig1s000MedR.pdf

214324Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov The primary objective of TIP-PH-101 was to evaluate the safety and tolerability of Treprostinil. Inhalation Powder (Tyvaso DPI) in subjects with ...

6. tyvasohcp.com tyvasohcp.com/ph-ild/efficacy-safety/increase-study/

TYVASO® INCREASE Study | PH-ILD View information on the INCREASE study, designed to assess the efficacy and safety of TYVASO® in patients with PH-ILD.