A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05147805
• Other study ID #: INS1009-202
• Secondary ID: 2021-001528-1620
• Status: Recruiting
• Phase: Phase 2
• Start date: August 24, 2022
• Est. completion date: March 31, 2024

Study information

• Verified date: March 2024
• Source: Insmed Incorporated
• Contact: Insmed Medical Information
• Phone: 1-844-446-7633
• Email: medicalinformation[@]insmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 99
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Treprostinil Palmitil
Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler.
• Placebo
Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler.

Locations

Country	Name	City	State
Argentina	ARG001	Córdoba
Argentina	ARG008	Cuiudad Autónoma De Buenos Aires
Argentina	ARG009	Quilmes	Buenos Aires
Argentina	ARG002	Rosario	Santa Fe
Argentina	ARG006	Rosario	Santa Fe
Argentina	ARG007	San Miguel de Tucuman	Tucumán
Australia	AUS003	Adelaide	South Australia
Australia	AUS002	Hobart	Tasmania
Australia	AUS004	Milton	Queensland
Australia	AUS005	New Lambton Heights	New South Wales
Australia	AUS001	Woolloongabba	Queensland
Austria	AUT002	Linz	Oberösterreich
Austria	AUT001	Wien
Belgium	BEL003	Anderlecht	Brussels
Belgium	BEL002	Leuven	Vlaams Brabant
Belgium	BEL001	Liège
Brazil	BRA003	Belo Horizonte	Minas Gerais
Brazil	BRA004	Belo Horizonte	Minas Gerais
Brazil	BRA002	Blumenau	Santa Catarina
Brazil	BRA007	Passo Fundo	Rio Grande Do Sul
Brazil	BRA006	Porto Alegre	Rio Grande Do Sul
Brazil	BRA001	São Paulo
Denmark	DNK001	Aarhus N	Central Jutland
Germany	GER007	Berlin
Germany	GER006	Dresden	Sachsen
Germany	GER005	Heidelberg	Baden-Württemberg
Germany	GER002	Lübeck	Schleswig-Holstein
Germany	GER003	Munich
Italy	ITA006	Milano	Lombardia
Italy	ITA005	Monza	Lombardia
Italy	ITA003	Napoli	Campania
Italy	ITA001	Palermo	Sicilia
Italy	ITA002	Pavia	Lombardia
Italy	ITA004	Roma
Japan	JPN001	Kagoshima-Shi	Kagosima
Japan	JPN007	Kurume-Shi	Hukuoka
Japan	JPN009	Nagasaki-Shi	Nagasaki
Japan	JPN002	Okayama-Shi	Okayama
Japan	JPN004	Sapporo-Shi	Hokkaidô
Japan	JPN005	Sapporo-Shi	Hokkaidô
Japan	JPN008	Shinjuku-Ku	Tokyo
Japan	JPN003	Suita-Shi	Ôsaka
Japan	JPN006	Tsukuba-Shi	Ibaraki
Malaysia	MYS003	Kajang	Selangor
Malaysia	MYS005	Kota Setar	Kedah
Malaysia	MYS002	Kuantan	Pahang
Malaysia	MYS004	Sungai Buloh	Selangor
Mexico	MEX005	Lomas De Guevara	Jalisco
Mexico	MEX003	Mexico
Mexico	MEX004	San Luis Potosí
Mexico	MEX001	Sertoma
Philippines	PHL002	Makati City
Philippines	PHL001	Quezon City	National Capital Region
Serbia	SRB001	Belgrade
Serbia	SRB003	Belgrade
Serbia	SRB004	Beograd	Belgrade
Spain	ESP002	Barcelona
Spain	ESP007	Las Palmas
Spain	ESP008	Madrid
Spain	ESP009	Oviedo	Asturias
Spain	ESP006	Palma de Mallorca	Baleares
Spain	ESP001	Santander	Cantabria
Spain	ESP003	Sevilla
Spain	ESP004	Toledo
Switzerland	CHE002	Lausanne	Vaud (fr)
United Kingdom	GBR001	Bath	Avon
United Kingdom	GBR002	Glasgow	Lanarkshire
United Kingdom	GBR004	London
United Kingdom	GBR006	London	London, City Of
United Kingdom	GBR003	Newcastle Upon Tyne	Tyne And Wear
United States	USA009	Atlanta	Georgia
United States	USA001	Chicago	Illinois
United States	USA006	Chicago	Illinois
United States	USA016	Dallas	Texas
United States	USA012	Denison	Texas
United States	USA008	Gainesville	Florida
United States	USA018	Houston	Texas
United States	USA013	Indianapolis	Indiana
United States	USA014	Iowa City	Iowa
United States	USA005	Jacksonville	Florida
United States	USA003	Kansas City	Kansas
United States	USA017	New York	New York
United States	USA102	New York	New York
United States	USA007	Orlando	Florida
United States	USA022	Scottsdale	Arizona
United States	USA011	Tampa	Florida
United States	USA021	Tucson	Arizona
United States	USA002	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
Insmed Incorporated

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Denmark,  Germany,  Italy,  Japan,  Malaysia,  Mexico,  Philippines,  Serbia,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Pulmonary Vascular Resistance at Week 16		Baseline to Week 16
Secondary	Change from Baseline in 6-Minute Walk Test Distance at Week 5, Week 10 and Week 16		Baseline and Week 5, Week 10 and Week 16
Secondary	Percent Change from Baseline in 6-Minute Walk Test Distance at Week 5, Week 10 and Week 16		Baseline and Week 5, Week 10 and Week 16
Secondary	Number of Participants Who Experience a Treatment-emergent Adverse Event (AE)		Day 1 up to Week 20
Secondary	Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Evaluations		Baseline to Week 16
Secondary	Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurements		Baseline to Week 16
Secondary	Number of Participants Who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements		Baseline to Week 16
Secondary	Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examinations		Baseline to Week 16
Secondary	Maximum Plasma Concentration (Cmax) of Treprostinil Palmitil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Maximum Plasma Concentration (Cmax) of Treprostinil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Time to Maximum Plasma Concentration (Tmax) of Treprostinil Palmitil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Time to Maximum Plasma Concentration (Tmax) of Treprostinil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-Dose (AUC24) of Treprostinil Palmitil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-Dose (AUC24) of Treprostinil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Area Under the Concentration-time Curve from Time 0 to Infinity (AUC8) of Treprostinil Palmitil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Area Under the Concentration-time Curve from Time 0 to Infinity (AUC8) of Treprostinil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Area Under the Concentration-time Curve from Time 0 to Last Measurable Concentration (AUClast) of Treprostinil Palmitil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Area Under the Concentration-time Curve from Time 0 to Last Measurable Concentration (AUClast) of Treprostinil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Apparent Total Clearance (CL/F) of Treprostinil Palmitil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Apparent Total Clearance (CL/F) of Treprostinil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Apparent Volume of Distribution After Non-Intravenous Administration (Vd/F) of Treprostinil Palmitil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Apparent Volume of Distribution After Non-Intravenous Administration (Vd/F) of Treprostinil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Elimination Half-Life (t1/2) of Treprostinil Palmitil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	Elimination Half-Life (t1/2) of Treprostinil		Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary	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		Baseline and Week 5, Week 10 and Week 16 or end of study