Treprostinil Palmitil for PAH

Not currently recruiting at 53 trial locations

Overseen By Insmed Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Insmed Incorporated

Must not be taking: Parenteral prostacyclin analogues

Disqualifiers: Heart disease, Thromboembolic disease, COVID-19, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Treprostinil Palmitil Inhalation Powder (TPIP) for individuals with pulmonary arterial hypertension (PAH), a condition that raises blood pressure in the lung arteries. The trial aims to determine if long-term use of TPIP is safe and tolerable. Suitable candidates have completed previous TPIP studies for PAH and can enroll within a year if the trial was not available immediately after their last study. As a Phase 3 trial, this study is the final step before FDA approval, allowing participants to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking inhaled or oral prostacyclin analogues (like Tyvaso or Orenitram) or receptor agonists (like selexipag) at least 24 hours before starting the study drug. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that Treprostinil Palmitil Inhalation Powder (TPIP) is likely to be safe for humans?

Research has shown that Treprostinil Palmitil Inhalation Powder (TPIP) is generally safe for people with pulmonary arterial hypertension (PAH). Most patients can use this treatment without serious issues. Common side effects include a mild cough and throat irritation, which are usually manageable and don't require stopping the treatment.

Earlier studies tested TPIP on patients with PAH, and the results were positive regarding safety. The treatment did not cause any severe or unexpected problems. The ongoing Phase 2 and Phase 3 trials suggest that earlier trials did not find major safety concerns, indicating the treatment might be safe for long-term use.

Overall, the evidence so far shows that TPIP is well-tolerated and does not cause significant side effects in most people. ^{1 2 3 4 5}

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

Treprostinil Palmitil Inhalation Powder (TPIP) is unique because it offers a new inhalation delivery method for treating pulmonary arterial hypertension (PAH), allowing for targeted delivery directly to the lungs. This is different from many current treatments, which are often administered orally or intravenously. Researchers are excited about TPIP because it potentially allows for more precise dosing with less systemic exposure, which may reduce side effects and improve patient outcomes. Plus, its formulation might enable a broader range of dosing options, which can be tailored to individual patient needs.

What evidence suggests that Treprostinil Palmitil Inhalation Powder (TPIP) might be an effective treatment for PAH?

Research has shown that Treprostinil Palmitil Inhalation Powder (TPIP), which participants in this trial will receive, holds promise for treating pulmonary arterial hypertension (PAH). One study found that TPIP significantly lowered resistance in the lung's blood vessels, a key factor in PAH. At Week 16, the treatment group had a mean ratio of 0.63 compared to 0.97 for the placebo group, indicating that TPIP helped blood flow more easily through the lungs. TPIP is already recognized as a treatment option for PAH and other lung issues, such as pulmonary hypertension due to lung disease. These findings suggest TPIP could be an effective option for those with PAH. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for men and women who have completed previous TPIP studies for PAH within the last year. They must not have started parenteral prostacyclin analogues since their last study but can join if they've stopped certain inhaled or oral treatments at least a day before starting this trial.

Inclusion Criteria

I completed a lead-in study less than a year ago and couldn't join the follow-up study then.

I completed a previous PAH study with INS1009.

Complete baseline screening assessments to confirm eligibility to participate if more than 30 days have elapsed since the end of the study visit in Study INS1009-201, INS1009-202, or any other lead-in PAH TPIP study

Exclusion Criteria

I have stopped my inhaled or oral prostacyclin treatments 24 hours before starting the study drug.

I started using injectable prostacyclin analogues after participating in specific clinical studies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

Participants undergo a 3-week titration period to adjust the dose of TPIP

3 weeks

Treatment

Participants receive TPIP once daily, with dose adjustments based on tolerance, for a total treatment period of 24 months

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Treprostinil Palmitil Inhalation Powder (TPIP)

Trial Overview

The study tests the long-term safety of Treprostinil Palmitil Inhalation Powder (TPIP) in people with Pulmonary Arterial Hypertension. Participants from earlier TPIP trials will either continue with TPIP or receive a placebo to compare effects over time.

How Is the Trial Designed?

Group I: Treprostinil Palmitil Inhalation Powder (TPIP) Experimental Treatment 2 Interventions

Participants who are not transitioning immediately from other TPIP studies:INS1009-201(NCT04791514), INS1009-202(NCT05147805) and other lead-in studies, will be given TPIP, once daily (QD), starting with 80 micrograms (μg), up-titrated to highest tolerated dose between 80 μg and 640 μg during 3-week titration period that maybe increased upto maximum dose of 1280 μg QD post initial titration, per investigator's assessment. Overall treatment period=24 months. Participants transitioning immediately from randomized blinded lead-in TPIP study and who previously received: 1. TPIP- will be given placebo QD(80 μg upto achieved TPIP dose from previous study)along with achieved TPIP dose from previous study in blinded manner during 3-week titration period. 2. Placebo- will be given TPIP QD (80 μg up to achieved placebo dose from previous study)along with achieved placebo dose from previous study in blinded manner during 3-week titration period.Overall treatment period=24 months.

Who Is Running the Clinical Trial?

Insmed Incorporated

Lead Sponsor

Trials

44

Recruited

7,600+

Published Research Related to This Trial

In a study using male Sprague-Dawley rats, inhaled treprostinil palmitil (TPIS) demonstrated sustained efficacy in inhibiting hypoxia-induced increases in right ventricular pulse pressure over 32 days, without evidence of tachyphylaxis, unlike continuous intravenous treprostinil (TRE) infusion which lost effectiveness after 16 days.

The lack of tachyphylaxis with TPIS is attributed to its local action in the lungs and lower plasma concentrations of TRE, suggesting that TPIS may provide a more consistent therapeutic effect for pulmonary vasodilation compared to traditional delivery methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treprostinil palmitil, an inhaled long-acting pulmonary vasodilator, does not show tachyphylaxis with daily dosing in rats. Chapman, RW., Li, Z., Chun, D., et al.[2021]

Treprostinil palmitil (TP), a long-acting prodrug of treprostinil, shows promise as a nebulized inhalation treatment for pulmonary arterial hypertension (PAH), maintaining effective drug levels in the lungs while minimizing systemic side effects compared to traditional treprostinil.

In preclinical studies, TP demonstrated superior efficacy in inhibiting pulmonary vasoconstriction and showed fewer respiratory-related side effects in humans, suggesting it could be a safer and more effective alternative to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of the biology of a long-acting inhaled treprostinil prodrug. Chapman, RW., Corboz, MR., Malinin, VS., et al.[2021]

Treprostinil palmitil (TP) inhalation powder (TPIP) shows consistent aerosol performance across various inhalation profiles, indicating its reliability for patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension due to interstitial lung disease (PH-ILD).

The emitted dose of TP from the TPIP capsules remains high (79-89%) at a 60 LPM inspiratory flow rate, suggesting effective delivery to the lungs, even with reduced inspiratory volumes and varying inhalation acceleration rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Inhalation Profile on Delivery of Treprostinil Palmitil Inhalation Powder. Gauani, H., Baker, T., Li, Z., et al.[2023]

Treprostinil palmitil (TP) has been successfully reformulated into a metered-dose inhaler (MDI) that maintains the pharmacokinetic and efficacy profile of the previously used nebulized formulation, making it a more convenient option for patients.

The optimized MDI formulation, TPIA-W, shows effective drug delivery and a prolonged efficacy lasting at least 12 hours, along with a higher cough threshold compared to the original treprostinil, indicating improved tolerability and potential for once-daily use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Characterization of Treprostinil Palmitil Inhalation Aerosol for the Investigational Treatment of Pulmonary Arterial Hypertension. Plaunt, AJ., Islam, S., Macaluso, T., et al.[2021]

Treprostinil palmitil inhalation powder (TPIP) was found to be well tolerated in healthy adults, with a high completion rate of 97.6% in the study, and most treatment-emergent adverse events (TEAEs) were mild, indicating a favorable safety profile for potential use in patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD).

The pharmacokinetics of TPIP showed linearity and supported a once-daily dosing regimen, with no severe or serious TEAEs reported, suggesting that TPIP could allow for higher tolerated doses compared to existing treprostinil formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Pharmacokinetics of Treprostinil Palmitil Inhalation Powder for Pulmonary Hypertension: A Phase 1, Randomized, Double-Blind, Single- and Multiple-Dose Study. Ismat, FA., Usansky, HH., Villa, R., et al.[2023]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05649748

An Extension Study of Treprostinil Palmitil Inhalation ...

The primary purpose of the study is to evaluate the safety and tolerability of the long-term use of TPIP in participants with PAH from studies INS1009-201 ...

2.

investor.insmed.com

investor.insmed.com/2025-06-10-Insmed-Announces-Positive-Topline-Results-from-Phase-2b-Study-of-Treprostinil-Palmitil-Inhalation-Powder-TPIP-as-Once-Daily-Therapy-in-Patients-with-Pulmonary-Arterial-Hypertension

Press Release - Investor Relations | Insmed Incorporated

Insmed Announces Positive Topline Results from Phase 2b Study of Treprostinil Palmitil Inhalation Powder (TPIP) as Once-Daily Therapy in ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07179380

NCT07179380 | Efficacy and Safety Study of Treprostinil ...

Participants will receive TPIP, once daily (QD), at a starting dose of 80 micrograms (μg) to maximum tolerated dose up to 1280 μg for 24 weeks.

4.

conferences.medicom-publishers.com

conferences.medicom-publishers.com/specialisation/respiratory/ers-2025/phase-2b-results-confirm-the-efficacy-of-treprostinil-palmitil-inhalation-powder-in-pulmonary-arterial-hypertension/

Phase 2b results confirm the efficacy of treprostinil palmitil ...

The study met its primary endpoint, with a least-squares mean ratio of pulmonary vascular resistance of 0.63 at Week 16 for TPIP versus 0.97 for ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11162632/

Therapeutic Potential of Treprostinil Inhalation Powder for ...

Inhaled treprostinil has been introduced as a treatment option in PAH and, more recently, pulmonary hypertension (PH) due to interstitial lung disease (PH-ILD).

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9525339/

Safety, Tolerability, and Pharmacokinetics of Treprostinil ...

This phase 1 study assessed the safety, tolerability, and pharmacokinetics of TP and treprostinil following single and multiple QD administrations of TPIP in ...

7.

tandfonline.com

tandfonline.com/doi/full/10.1080/17425247.2024.2395444

Treprostinil palmitil inhalation powder leverages ...

To determine key enzymes enabling treprostinil palmitil (TP) conversion to treprostinil and the main converting sites in the respiratory system.