Pulmonary Arterial Hypertension
Conditions
Keywords
Treprostinil Palmitil
Brief summary
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.
Interventions
Administered by oral inhalation, using a Plastiape capsule-based dry powder inhaler.
DRUGPlacebo
Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler
Sponsors
Insmed Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female participants who completed end of treatment study visit in Study INS1009-201, INS1009-202, or any other lead-in PAH TPIP study. Participants for whom the OLE study was not available at the time of their completion of the lead-in study are eligible for enrolment within one year of their lead-in end of treatment visit. * 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
* Initiation of parenteral administration of prostacyclin analogues (eg, TRE, epoprostenol) since the completion of studies INS1009-201, INS1009-202 or other TPIP studies. Initiation of inhaled prostacyclin analogues (eg, TRE \[Tyvaso\] or iloprost) and oral prostacyclin analogues (eg, TRE \[Orenitram\]) or receptor agonists (eg, selexipag) are permitted if stopped 24 hours prior to the start of study drug administration. * Any new ventricular or supraventricular tachyarrhythmia except for paroxysmal atrial fibrillation and any new symptomatic bradycardia. * New-onset of heart disease including left ventricular ejection fraction (LVEF) ≤40% or clinically significant valvular, constrictive, or symptomatic atherosclerotic heart disease (eg, stable angina, myocardial infarction, etc). * New evidence of thromboembolic disease as assessed by ventilation/perfusion (VQ) scan, pulmonary angiography, or pulmonary computed tomography (CT) scan. * Active and current symptomatic coronavirus disease 2019 (COVID-19) or previous severe disease and/or hospitalization due to COVID-19. * Interval organ transplantation. * New active liver disease or hepatic dysfunction. * Interval malignancy with exception of completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin. * Use of any investigational drug/device or participation in any investigational study within 30 days prior to screening, not including TPIP of the lead-in study. * Current use of cigarettes (as defined by Centers for Disease Control and Prevention \[CDC\]) or e-cigarettes: An adult who has smoked at least 100 cigarettes in his or her lifetime, who smokes either every day or some days. * Participants who currently inhale marijuana (recreational or medical). Note: Other inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Experience at Least one Treatment Emergent Adverse Event (TEAE) and TEAEs by Severity | From screening up to last follow up visit (Up to approximately 26 months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Pre-Open Label Extension (OLE) Baseline in 6-Minute Walk Distance (6MWD) | Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24 | — |
| Relative Change From Pre-OLE Baseline in 6MWD | Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24 | — |
| Change From Pre-OLE Baseline in the Concentration of N-Terminal Fragment B-Type Natriuretic Peptide (NT-proBNP) in Blood | Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24 | — |
| Change From Pre-OLE Baseline in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 Score | Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24 | — |
| Change From Pre-OLE Baseline in New York Heart Association/ World Health Organization (NYHA/WHO) Functional Capacity Class | Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24 | — |
| Annualized Clinical Worsening Event Rate | OLE Baseline (Day 1) up to Month 24 or early discontinuation | Annualized clinical worsening event rate is defined as the total number of clinical worsening events that occurred during the treatment period divided by the total number of participant-years during the treatment period. Clinical worsening events are one of the following: All-cause death, or onset of TEAE with a fatal outcome occurring ≤ 14 days after study drug discontinuation; Hospitalization for right heart failure (for \> 48 hours), heart-lung or lung transplant, or atrial septostomy; Addition (or increase in dose) of specified PAH-specific medications; Combined occurrence of events including ≥20% decrease in 6MWD, worsening WHO/NYHA functional capacity class, and appearance of or worsening of signs/symptoms of right heart failure from baseline. |
| Plasma Concentration Levels of Treprostinil Palmitil (TP) and Treprostinil (TRE) | OLE Baseline (Day 1), Months 6, 12, 18, and 24 | — |
Countries
Argentina, Austria, Belgium, Brazil, Denmark, Germany, Italy, Japan, Malaysia, Mexico, Philippines, Serbia, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Director
Insmed Incorporated
Outcome results
None listed