Inhaled Treprostinil for Pulmonary Fibrosis

(TETON-OLE Trial)

Enrolling by invitation at 211 trial locations

Overseen By United Therapeutics Global Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: United Therapeutics

Disqualifiers: Pregnancy, Lactation, Health risk, others

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

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: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests inhaled treprostinil to determine its safety and manageability for individuals with idiopathic pulmonary fibrosis or progressive pulmonary fibrosis. Pulmonary fibrosis scars the lungs, making breathing difficult. The trial uses a special inhaler to deliver treprostinil, which participants use multiple times daily. Those who participated in related studies and tolerated the treatment well are ideal candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, giving participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

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

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

Research has shown that inhaled treprostinil is usually well-tolerated by people with lung diseases. In studies involving patients with pulmonary hypertension (high blood pressure in the lungs), inhaled treprostinil improved exercise capacity and reduced the risk of symptom worsening by 39% compared to a placebo.

Although these studies did not specifically focus on pulmonary fibrosis, they suggest that the treatment is safe for individuals with lung-related conditions. The medicine is administered through a nebulizer, a device that converts liquid medicine into a mist for inhalation, allowing for accurate dosing.

In another study, inhaled treprostinil improved lung function and reduced disease flare-ups. While specific side effect data from these studies is unavailable, the regular use of this treatment for lung conditions indicates it is generally safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pulmonary fibrosis, which often include medications like pirfenidone and nintedanib, inhaled Treprostinil offers a new approach by being delivered directly to the lungs via an ultrasonic nebulizer. This method allows for targeted action at the site of the disease, potentially enhancing effectiveness and reducing systemic side effects. Researchers are excited about Treprostinil because it works by dilating blood vessels and improving blood flow in the lungs, which may alleviate symptoms more effectively than current options. Additionally, the inhalation route allows for rapid delivery and adjustment of dosage, providing flexibility and possibly faster symptom relief for patients.

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 will receive, can help treat lung diseases like idiopathic pulmonary fibrosis (IPF). Studies found that patients using this treatment could walk longer distances, as measured by the 6-minute walk distance (6MWD) test, starting as early as four weeks. Additionally, there was a 39% lower risk of their condition worsening compared to those not using it. Inhaled treprostinil has also improved lung function, measured by forced vital capacity (FVC), and reduced flare-ups of lung problems in similar conditions. These findings suggest that inhaled treprostinil may help manage symptoms and improve the quality of life for people with pulmonary fibrosis. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with idiopathic pulmonary fibrosis who previously participated in related studies (RIN-PF-301 or RIN-PF-303) and completed them or were active when the study ended. Participants must use effective contraception if of childbearing potential, be non-pregnant, non-lactating, reliable, and able to follow the study plan.

Inclusion Criteria

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

You were in a previous study and completed all the visits or were still in the study when it was stopped by the company.

In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.

Exclusion Criteria

Subject is pregnant or lactating.

In the opinion of the Investigator, enrollment in Study RIN-PF-302 would represent a risk to the subject's overall health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Extension

Participants receive inhaled treprostinil to evaluate long-term safety and tolerability

Up to 6 years

Visits at Week 4, Week 12, and every 12 weeks thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled Treprostinil
• Treprostinil Ultrasonic Nebulizer

Trial Overview The focus of this extension study is on assessing the long-term safety and tolerability of an inhaled medication called treprostinil using a nebulizer for patients with idiopathic pulmonary fibrosis.

How Is the Trial Designed?

Group I: Inhaled Treprostinil Experimental Treatment 2 Interventions

Treprostinil 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 to a target of 15 breaths QID or until the subject reaches their maximum clinically tolerated dose.

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

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]

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]

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]

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]

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 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]

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]

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]

Citations

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

United Therapeutics Corporation Announces TETON-2 ... While not statistically significant, both time to first acute exacerbation of IPF and overall survival at week 52 trended in favor of Tyvaso.

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. 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.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949789224000904

Study Design and Rationale for the TETON-PPF Phase 3, ... Inhaled treprostinil has demonstrated improvements in FVC and reduced exacerbations of underlying lung disease in patients with pulmonary hypertension ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04708782

NCT04708782 | Study of Efficacy and Safety of Inhaled ... Efficacy assessments include spirometry (FVC), time to clinical worsening, time to first acute exacerbation of IPF, overall survival, King's Brief Interstitial ...

6. 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.