Clinical trial NCT05147805: A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Arterial Hypertension
Official title: A Phase 2b, Randomized, Double-Blind, Multicenter, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Keywords: Treprostinil Palmitil
Pulmonary Arterial Hypertension
Lead sponsor: Insmed Incorporated
Sponsor class: INDUSTRY
First posted: 2021-12-07
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of the study is to assess the effect of treprostinil palmitil inhalation powder (TPIP) compared with placebo on pulmonary vascular resistance.


Eligibility criteria: Inclusion Criteria:

* Participants must be ≥ 18 to ≤ 75 years at the time of signing the informed consent form (ICF).
* Participants must have a diagnosis of World Health Organization (WHO) Group 1 Pulmonary Hypertension (PH) \[pulmonary arterial hypertension (PAH)\] in any of the following subtypes:

  1. Idiopathic
  2. Heritable
  3. Drug/toxin-induced or connective tissue disease (CTD)-associated PAH
  4. Congenital heart disease-related with simple systemic-to-pulmonary shunt at least 1 year following repair.
* PAH diagnosis for at least 3 months.
* Participants must be on stable PH therapy consisting of up to 2 medications from the following classes:

  1. Endothelin receptor antagonists (eg, ambrisentan, bosentan, macitentan)
  2. Phosphoesterase type 5 inhibitors (eg, sildenafil, tadalafil)
  3. Guanylate cyclase stimulator (eg, riociguat)
* No change in PH medications (eg, ambrisentan, bosentan, macitentan, sildenafil, tadalafil, riociguat) or dosage for at least 30 days prior to Screening.
* No change in long-term diuretic use or dosage for at least 30 days prior to Screening.
* Body Mass Index (BMI) within the range 18.0-37.0 kg/m\^2 (inclusive).
* Male participants: Male participants who are not sterile and have 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.
* Female participants: Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, (ie, post-tubal ligation for at least 12 months) 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.
* Male participants with pregnant or non-pregnant woman of childbearing potential partner must use a condom in order to avoid potential exposure to embryo/fetus.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.

Exclusion Criteria:

* History of PH other than idiopathic, hereditary, drug/toxin-induced, repaired simple congenital heart disease, or CTD-associated PAH (eg, complex, congenital heart disease-associated PAH, portal hypertension-associated PAH, PH belonging to Groups 2 through 5).
* Allergy, or documented hypersensitivity or contraindication, to TPIP or Treprostinil or mannitol (an excipient of the TPIP formulation).
* Any known ventricular or supraventricular tachyarrhythmia except for paroxysmal atrial fibrillation and 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 cardio-pulmonary rehabilitation program within 1 month of Screening Visit.
* Evidence of thromboembolic disease as assessed by ventilation-perfusion (VQ) scan, pulmonary angiography, or pulmonary computed tomography (CT) scan.
* Active liver disease or hepatic dysfunction.
* History of HIV infection.
* Established diagnosis of hepatitis B viral infection, or positive for hepatitis B surface antigen (HBsAg) at the time of Screening.
* Established diagnosis of hepatitis C viral infection at the time of screening.
* Active and current symptomatic coronavirus disease 2019 (COVID-19) or previous severe disease and/or hospitalization due to COVID-19.
* Use of live attenuated vaccines within 30 days of the Screening Visit.
* Participants with Down's Syndrome.
* History of abnormal bleeding or bruising.
* History of solid organ transplantation.
* Known or suspected immunodeficiency disorder, including history of invasive opportunistic infections (eg, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency, or prolonged infections suggesting an immune compromised status, as judged by the Investigator.
* History of alcohol or drug abuse within 6 months prior to Screening.
* Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements, in particular with 6-minute walk test (eg, angina pectoris, claudication, musculoskeletal disorder, need for walking aids).
* Participants with current or recent (past 30 days) lower respiratory tract infection.
* History of malignancy in the past 5 years, with exception of completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin.
* Change in PH medication (endothelin receptor agonists, phosphoesterase type 5 inhibitors, and guanylate cyclase stimulators or diuretics) between Screening and Baseline.
* Have participated in any other interventional clinical studies within 30 days prior to Screening.
* Current use of cigarettes (as defined by Centers for Disease Control and Prevention) or e-cigarettes.
* Participants who currently inhale marijuana (recreational or medical).
* Pregnant or breastfeeding.

Note: Other inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Change from Baseline in Pulmonary Vascular Resistance at Week 16
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: Change from Baseline in 6-Minute Walk Test Distance at Week 5, Week 10 and Week 16
timeFrame: Baseline and Week 5, Week 10 and Week 16
measure: Percent Change from Baseline in 6-Minute Walk Test Distance at Week 5, Week 10 and Week 16
timeFrame: Baseline and Week 5, Week 10 and Week 16
measure: Number of Participants Who Experience a Treatment-emergent Adverse Event (AE)
timeFrame: Day 1 up to Week 20
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Evaluations
timeFrame: Baseline to Week 16
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurements
timeFrame: Baseline to Week 16
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements
timeFrame: Baseline to Week 16
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examinations
timeFrame: Baseline to Week 16
measure: Maximum Plasma Concentration (Cmax) of Treprostinil Palmitil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Maximum Plasma Concentration (Cmax) of Treprostinil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Time to Maximum Plasma Concentration (Tmax) of Treprostinil Palmitil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Time to Maximum Plasma Concentration (Tmax) of Treprostinil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-Dose (AUC24) of Treprostinil Palmitil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-Dose (AUC24) of Treprostinil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Area Under the Concentration-time Curve from Time 0 to Infinity (AUC∞) of Treprostinil Palmitil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Area Under the Concentration-time Curve from Time 0 to Infinity (AUC∞) of Treprostinil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Area Under the Concentration-time Curve from Time 0 to Last Measurable Concentration (AUClast) of Treprostinil Palmitil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Area Under the Concentration-time Curve from Time 0 to Last Measurable Concentration (AUClast) of Treprostinil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Apparent Total Clearance (CL/F) of Treprostinil Palmitil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Apparent Total Clearance (CL/F) of Treprostinil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Apparent Volume of Distribution After Non-Intravenous Administration (Vd/F) of Treprostinil Palmitil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Apparent Volume of Distribution After Non-Intravenous Administration (Vd/F) of Treprostinil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Elimination Half-Life (t1/2) of Treprostinil Palmitil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Elimination Half-Life (t1/2) of Treprostinil
timeFrame: Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
measure: Change from Baseline in the Concentration of N-Terminal-Pro Hormone Brain Natriuretic Peptide (NT-proBNP) Levels at Week 5, Week 10 and Week 16
timeFrame: Baseline and Week 5, Week 10 and Week 16 or end of study
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: USA025
state: Arizona
city: Scottsdale
country: United States
facility: USA022
state: Arizona
city: Tucson
country: United States
facility: USA021
state: Arizona
city: Sacramento
country: United States
facility: USA023
state: California
city: West Hollywood
country: United States
facility: USA002
state: California
city: Gainesville
country: United States
facility: USA008
state: Florida
city: Jacksonville
country: United States
facility: USA005
state: Florida
city: Orlando
country: United States
facility: USA007
state: Florida
city: Tampa
country: United States
facility: USA011
state: Florida
city: Winter Park
country: United States
facility: USA010
state: Florida
city: Atlanta
country: United States
facility: USA009
state: Georgia
city: Chicago
country: United States
facility: USA006
state: Illinois
city: Chicago
country: United States
facility: USA001
state: Illinois
city: Indianapolis
country: United States
facility: USA013
state: Indiana
city: Iowa City
country: United States
facility: USA014
state: Iowa
city: Kansas City
country: United States
facility: USA003
state: Kansas
city: New York
country: United States
facility: USA102
state: New York
city: New York
country: United States
facility: USA017
state: New York
city: Dallas
country: United States
facility: USA016
state: Texas
city: Denison
country: United States
facility: USA012
state: Texas
city: Houston
country: United States
facility: USA018
state: Texas
city: Quilmes
country: Argentina
facility: ARG009
state: Buenos Aires
city: Rosario
country: Argentina
facility: ARG002
state: Santa Fe
city: Rosario
country: Argentina
facility: ARG006
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: ARG007
state: Tucumán
city: Cuiudad Autónoma De Buenos Aires
country: Argentina
facility: ARG008
city: Córdoba
country: Argentina
facility: ARG004
city: Córdoba
country: Argentina
facility: ARG001
city: New Lambton Heights
country: Australia
facility: AUS005
state: New South Wales
city: Milton
country: Australia
facility: AUS004
state: Queensland
city: Woolloongabba
country: Australia
facility: AUS001
state: Queensland
city: Adelaide
country: Australia
facility: AUS003
state: South Australia
city: Hobart
country: Australia
facility: AUS002
state: Tasmania
city: Linz
country: Austria
facility: AUT002
state: Oberösterreich
city: Wien
country: Austria
facility: AUT001
city: Anderlecht
country: Belgium
facility: BEL003
state: Brussels
city: Leuven
country: Belgium
facility: BEL002
state: Vlaams Brabant
city: Liège
country: Belgium
facility: BEL001
city: Belo Horizonte
country: Brazil
facility: BRA003
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: BRA004
state: Minas Gerais
city: Passo Fundo
country: Brazil
facility: BRA007
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: BRA006
state: Rio Grande Do Sul
city: Blumenau
country: Brazil
facility: BRA002
state: Santa Catarina
city: São Paulo
country: Brazil
facility: BRA001
city: Aarhus N
country: Denmark
facility: DNK001
state: Central Jutland
city: Heidelberg
country: Germany
facility: GER005
state: Baden-Württemberg
city: Halle
country: Germany
facility: GER001
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: GER006
state: Sachsen
city: Lübeck
country: Germany
facility: GER002
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GER007
city: Munich
country: Germany
facility: GER003
city: Napoli
country: Italy
facility: ITA003
state: Campania
city: Milano
country: Italy
facility: ITA006
state: Lombardia
city: Monza
country: Italy
facility: ITA005
state: Lombardia
city: Pavia
country: Italy
facility: ITA002
state: Lombardia
city: Palermo
country: Italy
facility: ITA001
state: Sicilia
city: Roma
country: Italy
facility: ITA004
city: Sapporo-Shi
country: Japan
facility: JPN005
state: Hokkaidô
city: Sapporo-Shi
country: Japan
facility: JPN004
state: Hokkaidô
city: Kurume-Shi
country: Japan
facility: JPN007
state: Hukuoka
city: Tsukuba-Shi
country: Japan
facility: JPN006
state: Ibaraki
city: Kagoshima-Shi
country: Japan
facility: JPN001
state: Kagosima
city: Nagasaki-Shi
country: Japan
facility: JPN009
state: Nagasaki
city: Okayama-Shi
country: Japan
facility: JPN002
state: Okayama
city: Shinjuku-Ku
country: Japan
facility: JPN008
state: Tokyo
city: Suita-Shi
country: Japan
facility: JPN003
state: Ôsaka
city: Kota Setar
country: Malaysia
facility: MYS005
state: Kedah
city: Kuantan
country: Malaysia
facility: MYS002
state: Pahang
city: Kajang
country: Malaysia
facility: MYS003
state: Selangor
city: Sungai Buloh
country: Malaysia
facility: MYS004
state: Selangor
city: Ciudad de México
country: Mexico
facility: MEX003
state: Distrito Federal
city: Lomas De Guevara
country: Mexico
facility: MEX005
state: Jalisco
city: San Luis Potosí
country: Mexico
facility: MEX004
city: Sertoma
country: Mexico
facility: MEX001
city: Quezon City
country: Philippines
facility: PHL001
state: National Capital Region
city: Makati City
country: Philippines
facility: PHL002
city: Beograd
country: Serbia
facility: SRB004
state: Belgrade
city: Belgrade
country: Serbia
facility: SRB001
city: Beograd
country: Serbia
facility: SRB003
city: Palma de Mallorca
country: Spain
facility: ESP006
state: Baleares
city: Santander
country: Spain
facility: ESP001
state: Cantabria
city: Barcelona
country: Spain
facility: ESP002
city: Las Palmas
country: Spain
facility: ESP007
city: Madrid
country: Spain
facility: ESP008
city: Sevilla
country: Spain
facility: ESP003
city: Toledo
country: Spain
facility: ESP004
city: Lausanne
country: Switzerland
facility: CHE002
state: Vaud (fr)
city: Bath
country: United Kingdom
facility: GBR001
state: Avon
city: Glasgow
country: United Kingdom
facility: GBR002
state: Lanarkshire
city: London
country: United Kingdom
facility: GBR006
state: London, City Of
city: Newcastle Upon Tyne
country: United Kingdom
facility: GBR003
state: Tyne And Wear
city: London
country: United Kingdom
facility: GBR004
Study officials:
References: