Clinical trial NCT05176951: A Study to Evaluate the Safety and Tolerability of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease
Official title: A Phase 2, Randomized, Double-Blind, Multicenter, Placebo-Controlled Study to Evaluate the Safety and Tolerability of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Hypertension
Keywords: Pulmonary Hypertension
Interstitial Lung Disease
Treprostinil Palmitil
Lead sponsor: Insmed Incorporated
Sponsor class: INDUSTRY
First posted: 2022-01-04
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and tolerability of treprostinil palmitil inhalation powder (TPIP) compared with placebo


Eligibility criteria: Inclusion Criteria:

* Males and females must be ≥ 18 to ≤ 80 years of age at the time of signing the informed consent form (ICF).
* Diagnosis of pulmonary hypertension (PH) associated with interstitial lung disease (ILD) (including idiopathic interstitial pneumonia \[IIP\], idiopathic pulmonary fibrosis \[IPF\], connective tissue disease \[CTD\], sarcoidosis).
* Male and female participants must use contraceptives that are consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Male participants:

Male participants who are not sterile, with female partners of childbearing potential, must be using effective contraception from Day 1 to at least 90 days after the last dose of study drug.

Male participants with women of child bearing potential (WOCBP) partner must use a condom in order to avoid potential exposure to embryo/fetus.

- Female participants: Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, (ie,hysterectomy and/or bilateral salpingo-oophorectomy) or using highly effective contraception methods (ie, methods that alone or in combination achieve \<1% unintended pregnancy rates per year when used consistently and correctly) from Day 1 to at least 90 days after the last dose of study drug.

- Capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

* Primary diagnosis of chronic obstructive pulmonary disease (COPD).
* Allergy, or documented hypersensitivity or contraindication to TPIP or treprostinil (TRE) or mannitol (an excipient of the TPIP formulation).
* Received or currently treated with riociguat, endothelin receptor antagonists, selexipag, phosphodiesterase 5 (PDE5) inhibitors and/or prostacyclin analogues within 30 days prior to Screening.
* Started therapy with pirfenidone or nintedanib \< 90 days prior to Screening, OR, if already receiving either medication, there is a dose change within 30 days of Screening Visit.
* Any known ventricular or supraventricular tachyarrhythmia (except for paroxysmal atrial fibrillation), and/or any symptomatic bradycardia.
* History 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).
* Participation in a cardiopulmonary rehabilitation program within 30 days of the first Screening Visit. Participation in the maintenance program of a cardiopulmonary rehabilitation program is allowed.
* Acutely decompensated heart failure within 30 days of Screening Visit.
* Active and current symptomatic coronavirus disease 2019 (COVID-19) and/or previous diagnosis of moderate to severe disease, or hospitalization due to COVID-19.
* Supplemental oxygen requirement \> 10L/min at rest at Screening.
* Exacerbation of underlying lung disease or active pulmonary or upper respiratory infection within 30 days of the first dose of study drug (may be rescreened at appropriate time).
* Current or recent (past 30 days) lower respiratory tract infection (may be rescreened at appropriate time).
* Any form of congenital heart disease or congenital heart defect (repaired or unrepaired) other than a patent foramen ovale.
* History of alcohol or drug abuse within 6 months prior to Screening.
* Current use of cigarettes (as defined by Center for Disease Control (CDC)) or e-cigarettes: An adult who has smoked at least 100 cigarettes in his or her lifetime and who currently smokes either every day or some days.
* Participants who currently inhale marijuana (recreational or medical).
* Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements, in particular with 6-minute walk test (6MWT) (eg, angina pectoris, claudication, musculoskeletal disorder, need for walking aids).

Primary outcomes:
measure: Number of Participants Who Experience Any Number of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 140
measure: Number of Participants Who Experience Any Number of Serious Adverse Events (SAEs)
timeFrame: Up to Day 140
measure: Change from Baseline in Saturation of Peripheral Capillary Oxygenation (SpO2) Levels
timeFrame: Pre-, during, and post- 6-minute walk test (6MWT) at Baseline, Week 5, Week 10, and Week 16
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Treprostinil Palmitil
timeFrame: Day 1 to Week 16
measure: Cmax of Treprostinil
timeFrame: Day 1 to Week 16
measure: Time to Maximum Plasma Concentration (Tmax) of Treprostinil Palmitil
timeFrame: Day 1 to Week 16
measure: Tmax of Treprostinil
timeFrame: Day 1 to Week 16
measure: Area Under Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUCtau) of Treprostinil Palmitil
timeFrame: Day 1 to Week 16
measure: AUCtau of Treprostinil
timeFrame: Day 1 to Week 16
measure: Area Under Concentration-time Curve From 0 to Infinity (AUC∞) of Treprostinil Palmitil
timeFrame: Day 1 to Week 16
measure: AUC∞ of Treprostinil
timeFrame: Day 1 to Week 16
measure: Area Under Concentration-time Curve From Time 0 to Last Measurable Concentration (AUClast) of Treprostinil Palmitil
timeFrame: Day 1 to Week 16
measure: AUClast of Treprostinil
timeFrame: Day 1 to Week 16
measure: Apparent Total Clearance (CL/F) of Treprostinil Palmitil
timeFrame: Day 1 to Week 16
measure: CL/F of Treprostinil
timeFrame: Day 1 to Week 16
measure: Elimination Half-life (t1/2) of Treprostinil Palmitil
timeFrame: Day 1 to Week 16
measure: t1/2 of Treprostinil
timeFrame: Day 1 to Week 16
measure: Apparent Volume of Distribution After Terminal Phase (Vd/F) of Treprostinil Palmitil
timeFrame: Day 1 to Week 16
measure: Vd/F of Treprostinil
timeFrame: Day 1 to Week 16
Other outcomes:
Locations:
city: Barracas
country: Argentina
facility: ARG003
state: Ciudad Autónoma De BuenosAires
city: Rosario
country: Argentina
facility: ARG001
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: ARG008
city: Camperdown
country: Australia
facility: AUS003
state: New South Wales
city: Macquarie Park
country: Australia
facility: AUS005
state: New South Wales
city: Liège
country: Belgium
facility: BEL002
city: Heidelberg
country: Germany
facility: GER006
state: Baden-Württemberg
city: Gießen
country: Germany
facility: GER010
state: Hessen
city: Essen
country: Germany
facility: GER003
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: GER001
state: Sachsen
city: Berlin
country: Germany
facility: GER002
city: Berlin
country: Germany
facility: GER012
city: Munich
country: Germany
facility: GER004
city: Napoli
country: Italy
facility: ITA003
state: Campania
city: Milano
country: Italy
facility: ITA004
state: Lombardia
city: Monza
country: Italy
facility: ITA002
state: Lombardia
city: Palermo
country: Italy
facility: ITA001
state: Sicilia
city: Oviedo
country: Spain
facility: ESP007
state: Asturias
city: Palma de Mallorca
country: Spain
facility: ESP003
state: Baleares
city: Barcelona
country: Spain
facility: ESP010
city: Barcelona
country: Spain
facility: ESP005
city: las Palmas de Gran Canaria
country: Spain
facility: ESP006
city: Santiago de Compostela
country: Spain
facility: ESP009
city: Glasgow
country: United Kingdom
facility: GBR003
state: Lanarkshire
city: Sheffield
country: United Kingdom
facility: GBR001
state: Yorkshire
Study officials:
References: