Inhaled Treprostinil for Pulmonary Fibrosis

(TETON-OLE Trial)

Recruiting at 186 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

792 Participants Needed

Trial Summary

What is the purpose of this trial?

Study RIN-PF-302 is designed to evaluate the long-term safety and tolerability of inhaled treprostinil in subjects with idiopathic pulmonary fibrosis.

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 inhaled treprostinil safe for humans?

Inhaled treprostinil, used for conditions like pulmonary arterial hypertension, has been shown to be generally safe in humans. Common side effects include cough, throat irritation, and nasal discomfort, but it is well tolerated overall. ^{1 2 3 4 5}

What makes the drug Inhaled Treprostinil unique for treating pulmonary fibrosis?

Inhaled Treprostinil is unique for treating pulmonary fibrosis because it is administered through inhalation, which directly targets the lungs, potentially improving breathing and reducing symptoms more effectively than oral or injectable treatments. This method of delivery is particularly beneficial for lung conditions, as it allows the medication to act directly where it is needed. ^{6 7 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Tyvaso DPI: Drug-device characteristics and patient clinical considerations. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

An observational study of inhaled-treprostinil respiratory-related safety in patients with pulmonary arterial hypertension. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A Comprehensive Review of Treprostinil Pharmacokinetics via Four Routes of Administration. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Patient safety challenges in treprostinil therapy. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Comparative bioavailability of inhaled treprostinil administered as LIQ861 and Tyvaso® in healthy subjects. [2021]

6. Germany 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. [2017]

7. India pubmed.ncbi.nlm.nih.gov

Treating overactive bladder symptoms after transurethral prostatic surgery for benign prostatic hyperplasia - Which medication to choose? [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

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

9. United States pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial of Vesicare™ (solifenacin) in the treatment of urinary incontinence after radical prostatectomy. [2018]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[A trial of the use of finasteride and terazosin in patients with benign prostatic hyperplasia]. [2013]