Treprostinil Palmitil for PAH

Recruiting at 45 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

91 Participants Needed

Trial Summary

What is the purpose of this trial?

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 (NCT04791514), INS1009-202 (NCT05147805) and other lead-in studies of TPIP in participants with PAH.

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.

What data supports the effectiveness of the drug Treprostinil Palmitil Inhalation Powder (TPIP) for treating pulmonary arterial hypertension (PAH)?

Research shows that Treprostinil Palmitil, a long-acting form of the drug treprostinil, can effectively reduce lung blood pressure without causing tachyphylaxis (a decrease in response to a drug after repeated use) in animal studies. Additionally, it has been shown to maintain high concentrations in the lungs with fewer side effects compared to other forms of treprostinil, and it has demonstrated effectiveness in reducing lung inflammation and remodeling in animal models. ^{1 2 3 4 5}

Is Treprostinil Palmitil safe for humans?

Treprostinil Palmitil, in its inhaled form, has been studied for safety in humans. A Phase 1 study showed it was generally well-tolerated with fewer respiratory-related side effects compared to other forms of treprostinil. It also demonstrated a lower concentration in the blood, which may reduce side effects. ^{1 2 3 4 5}

What makes the drug Treprostinil Palmitil Inhalation Powder (TPIP) unique for treating pulmonary arterial hypertension (PAH)?

Treprostinil Palmitil Inhalation Powder (TPIP) is unique because it is a long-acting inhaled prodrug that provides sustained release of treprostinil in the lungs, potentially allowing for once-daily dosing and higher tolerated doses compared to other treprostinil formulations. Unlike continuous intravenous or subcutaneous treprostinil, TPIP does not show tachyphylaxis (a reduced response to a drug over time) with daily use, which means it may not require frequent dose increases to remain effective. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

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

An overview of the biology of a long-acting inhaled treprostinil prodrug. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Inhalation Profile on Delivery of Treprostinil Palmitil Inhalation Powder. [2023]

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

Development and Characterization of Treprostinil Palmitil Inhalation Aerosol for the Investigational Treatment of Pulmonary Arterial Hypertension. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Treprostinil palmitil, an inhaled long-acting pulmonary vasodilator, does not show tachyphylaxis with daily dosing in rats. [2021]

5. United States 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. [2023]