An Extension Study of Treprostinil Palmitil Inhalation Powder (TPIP) for Pulmonary Arterial Hypertension (PAH)

JRCT ID: jRCT2061220089

Registered date:30/01/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Pulmonary Arterial Hypertension
• Date of first enrollment: 07/03/2023
• Target sample size: 100
• Countries of recruitment: United States,Japan,Argentina,Japan,Austria,Japan,Denmark,Japan,Mexico,Japan,Phillipines,Japan,Brazil,Japan,Germany,Japan,Italy,Japan,Malaysia,Japan,Spain,Japan,United Kingdom,Japan,Serbia,Japan
• Study type: Interventional
• Intervention(s): 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, up-titrated to highest tolerated dose between 80 micrograms and 640 micrograms during 3-week titration period that maybe increased upto maximum dose of 1280 micrograms QD post initial titration, per investigator's assessment. Overall treatment period=84 months. Participants transitioning immediately from randomized blinded lead-in TPIP study and who previously received: 1.TPIP- will be given placebo QD (80 micrograms 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 micrograms up to achieved placebo dose from previous study) along with achieved placebo dose from previous study in blinded manner during 3-week titration period.

Outcome(s)

• Primary Outcome: 1. Number of Participants Who Experience at Least one Treatment Emergent Adverse Event (TEAE) and TEAEs by Severity up to Approximately 85 Months

Secondary Outcome

"1. Absolute Change From Pre-Open Label Extension (OLE) Baseline to Month 6, Month 12, Month 18, Month 24, Month 30, Month 36, Month 42, Month 48, Month 54, Month 60, Month 66, Month 72, Month 78 and Month 84 in 6-Minute Walk Distance (6MWD)
2. Relative Change From Pre-OLE Baseline to Month 6, Month 12, Month 18, Month 24, Month 30, Month 36, Month 42, Month 48, Month 54, Month 60, Month 66, Month 72, Month 78 and Month 84 in 6MWD
3. Change From Pre-OLE Baseline to Month 6, Month 12, Month 18, Month 24, Month 36, Month 48, Month 60, Month 72 and Month 84 in the Concentration of N-Terminal Fragment B-Type Natriuretic Peptide (NT-proBNP) in Blood
4. Change From Pre-OLE Baseline to Month 6, Month 12, Month 18, and Month 24 in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 Score
5. Change From Pre-OLE Baseline to Month 6, Month 12, Month 18, Month 24, Month 30, Month 36, Month 42, Month 48, Month 54, Month 60, Month 66, Month 72, Month 78 and Month 84 in New York Heart Association/ World Health Organization (NYHA/WHO) Functional Capacity Class
6. Annualized Clinical Worsening Event Rate From Baseline up to Month 84 or Early Discontinuation
7. Plasma Concentration Levels of TP (Treprostinil Palmitil) and TRE (Treprostinil)"

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. 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.
2. 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.

Exclude criteria

1. 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.
2. Any new ventricular or supraventricular tachyarrhythmia except for paroxysmal atrial fibrillation and any new symptomatic bradycardia.
3. New-onset of heart disease including left ventricular ejection fraction (LVEF) less than or equal to 40% or clinically significant valvular, constrictive, or symptomatic atherosclerotic heart disease (eg, stable angina, myocardial infarction, etc).
4. New evidence of thromboembolic disease as assessed by ventilation/perfusion (VQ) scan, pulmonary angiography, or pulmonary computed tomography (CT) scan.
5. Active and current symptomatic coronavirus disease 2019 (COVID-19) or previous severe disease and/or hospitalization due to COVID-19.
6. Interval organ transplantation.
7. New active liver disease or hepatic dysfunction.
8. 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.
9. 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.
10. 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.
11. Participants who currently inhale marijuana (recreational or medical).
Note: Other inclusion/exclusion criteria may apply.

Related Information

• Primary Sponsor: Fraz Ismat
• Secondary ID(s): 2022-001951-18,NCT05649748,2023-505539-11-00