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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05147805




Registration number
NCT05147805
Ethics application status
Date submitted
24/11/2021
Date registered
7/12/2021

Titles & IDs
Public title
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Arterial Hypertension
Scientific 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
Secondary ID [1] 0 0
2021-001528-16
Secondary ID [2] 0 0
INS1009-202
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Treprostinil Palmitil
Treatment: Drugs - Placebo

Experimental: Treprostinil Palmitil Inhalation Powder - Participants will be administered TPIP once per day at a starting dose of 80 micrograms (µg). Participants will be up-titrated to the highest tolerated dose for each individual participant of between 80 µg and 640 µg during the initial 3 weeks of treatment. The overall treatment period will be 16 weeks.

Placebo comparator: Placebo - Participants will be administered a placebo matching TPIP once per day for 16 weeks.


Treatment: Drugs: Treprostinil Palmitil
Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler.

Treatment: Drugs: Placebo
Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in Pulmonary Vascular Resistance at Week 16
Timepoint [1] 0 0
Baseline to Week 16
Secondary outcome [1] 0 0
Change from Baseline in 6-Minute Walk Test Distance at Week 5, Week 10 and Week 16
Timepoint [1] 0 0
Baseline and Week 5, Week 10 and Week 16
Secondary outcome [2] 0 0
Percent Change from Baseline in 6-Minute Walk Test Distance at Week 5, Week 10 and Week 16
Timepoint [2] 0 0
Baseline and Week 5, Week 10 and Week 16
Secondary outcome [3] 0 0
Number of Participants Who Experience a Treatment-emergent Adverse Event (AE)
Timepoint [3] 0 0
Day 1 up to Week 20
Secondary outcome [4] 0 0
Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Evaluations
Timepoint [4] 0 0
Baseline to Week 16
Secondary outcome [5] 0 0
Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurements
Timepoint [5] 0 0
Baseline to Week 16
Secondary outcome [6] 0 0
Number of Participants Who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements
Timepoint [6] 0 0
Baseline to Week 16
Secondary outcome [7] 0 0
Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examinations
Timepoint [7] 0 0
Baseline to Week 16
Secondary outcome [8] 0 0
Maximum Plasma Concentration (Cmax) of Treprostinil Palmitil
Timepoint [8] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [9] 0 0
Maximum Plasma Concentration (Cmax) of Treprostinil
Timepoint [9] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [10] 0 0
Time to Maximum Plasma Concentration (Tmax) of Treprostinil Palmitil
Timepoint [10] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [11] 0 0
Time to Maximum Plasma Concentration (Tmax) of Treprostinil
Timepoint [11] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [12] 0 0
Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-Dose (AUC24) of Treprostinil Palmitil
Timepoint [12] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [13] 0 0
Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-Dose (AUC24) of Treprostinil
Timepoint [13] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [14] 0 0
Area Under the Concentration-time Curve from Time 0 to Infinity (AUC8) of Treprostinil Palmitil
Timepoint [14] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [15] 0 0
Area Under the Concentration-time Curve from Time 0 to Infinity (AUC8) of Treprostinil
Timepoint [15] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [16] 0 0
Area Under the Concentration-time Curve from Time 0 to Last Measurable Concentration (AUClast) of Treprostinil Palmitil
Timepoint [16] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [17] 0 0
Area Under the Concentration-time Curve from Time 0 to Last Measurable Concentration (AUClast) of Treprostinil
Timepoint [17] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [18] 0 0
Apparent Total Clearance (CL/F) of Treprostinil Palmitil
Timepoint [18] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [19] 0 0
Apparent Total Clearance (CL/F) of Treprostinil
Timepoint [19] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [20] 0 0
Apparent Volume of Distribution After Non-Intravenous Administration (Vd/F) of Treprostinil Palmitil
Timepoint [20] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [21] 0 0
Apparent Volume of Distribution After Non-Intravenous Administration (Vd/F) of Treprostinil
Timepoint [21] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [22] 0 0
Elimination Half-Life (t1/2) of Treprostinil Palmitil
Timepoint [22] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [23] 0 0
Elimination Half-Life (t1/2) of Treprostinil
Timepoint [23] 0 0
Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Secondary outcome [24] 0 0
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
Timepoint [24] 0 0
Baseline and Week 5, Week 10 and Week 16 or end of study

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/08/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2025
Actual
Sample size
Target
99
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
AUS001 - Woolloongabba
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Argentina
State/province [12] 0 0
Santa Fe
Country [13] 0 0
Argentina
State/province [13] 0 0
Tucumán
Country [14] 0 0
Argentina
State/province [14] 0 0
Cuiudad Autónoma De Buenos Aires
Country [15] 0 0
Argentina
State/province [15] 0 0
Córdoba
Country [16] 0 0
Austria
State/province [16] 0 0
Oberösterreich
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Belgium
State/province [18] 0 0
Brussels
Country [19] 0 0
Belgium
State/province [19] 0 0
Vlaams Brabant
Country [20] 0 0
Belgium
State/province [20] 0 0
Liège
Country [21] 0 0
Brazil
State/province [21] 0 0
Minas Gerais
Country [22] 0 0
Brazil
State/province [22] 0 0
Rio Grande Do Sul
Country [23] 0 0
Brazil
State/province [23] 0 0
Santa Catarina
Country [24] 0 0
Brazil
State/province [24] 0 0
São Paulo
Country [25] 0 0
Denmark
State/province [25] 0 0
Central Jutland
Country [26] 0 0
Germany
State/province [26] 0 0
Baden-Württemberg
Country [27] 0 0
Germany
State/province [27] 0 0
Sachsen
Country [28] 0 0
Germany
State/province [28] 0 0
Schleswig-Holstein
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Munich
Country [31] 0 0
Italy
State/province [31] 0 0
Campania
Country [32] 0 0
Italy
State/province [32] 0 0
Lombardia
Country [33] 0 0
Italy
State/province [33] 0 0
Sicilia
Country [34] 0 0
Italy
State/province [34] 0 0
Roma
Country [35] 0 0
Japan
State/province [35] 0 0
Hokkaidô
Country [36] 0 0
Japan
State/province [36] 0 0
Hukuoka
Country [37] 0 0
Japan
State/province [37] 0 0
Ibaraki
Country [38] 0 0
Japan
State/province [38] 0 0
Kagosima
Country [39] 0 0
Japan
State/province [39] 0 0
Nagasaki
Country [40] 0 0
Japan
State/province [40] 0 0
Okayama
Country [41] 0 0
Japan
State/province [41] 0 0
Tokyo
Country [42] 0 0
Japan
State/province [42] 0 0
Ôsaka
Country [43] 0 0
Malaysia
State/province [43] 0 0
Kedah
Country [44] 0 0
Malaysia
State/province [44] 0 0
Pahang
Country [45] 0 0
Malaysia
State/province [45] 0 0
Selangor
Country [46] 0 0
Mexico
State/province [46] 0 0
Distrito Federal
Country [47] 0 0
Mexico
State/province [47] 0 0
Jalisco
Country [48] 0 0
Mexico
State/province [48] 0 0
San Luis Potosí
Country [49] 0 0
Mexico
State/province [49] 0 0
Sertoma
Country [50] 0 0
Philippines
State/province [50] 0 0
National Capital Region
Country [51] 0 0
Philippines
State/province [51] 0 0
Makati City
Country [52] 0 0
Serbia
State/province [52] 0 0
Belgrade
Country [53] 0 0
Serbia
State/province [53] 0 0
Beograd
Country [54] 0 0
Spain
State/province [54] 0 0
Baleares
Country [55] 0 0
Spain
State/province [55] 0 0
Cantabria
Country [56] 0 0
Spain
State/province [56] 0 0
Barcelona
Country [57] 0 0
Spain
State/province [57] 0 0
Las Palmas
Country [58] 0 0
Spain
State/province [58] 0 0
Madrid
Country [59] 0 0
Spain
State/province [59] 0 0
Sevilla
Country [60] 0 0
Spain
State/province [60] 0 0
Toledo
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Avon
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Lanarkshire
Country [63] 0 0
United Kingdom
State/province [63] 0 0
London, City Of
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Tyne And Wear
Country [65] 0 0
United Kingdom
State/province [65] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Insmed Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Insmed Medical Information
Address 0 0
Country 0 0
Phone 0 0
1-844-446-7633
Fax 0 0
Email 0 0
medicalinformation@insmed.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05147805