Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension, Treprostinil Palmitil Inhalation Powder, Treprostinil Palmitil
Brief summary
The main purpose of this study is to evaluate the safety and tolerability of single dose of treprostinil palmitil inhalation powder (TPIP) in participants with pulmonary arterial hypertension (PAH).
Interventions
Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler
Sponsors
Insmed Incorporated
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must be ≥ 18 years of age at the time of signing the informed consent * Participants must have a diagnosis of World Health Organization Group 1 Pulmonary Hypertension (PH) (PAH) with the following characteristics 1. Etiology of idiopathic, heritable, drug/toxin-induced or connective tissue disease (CTD)-related PAH 2. Right heart catheterization with the following hemodynamic findings: * Mean pulmonary arterial pressure (mPAP) \> 20 mmHg at rest, * Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg, and * Pulmonary vascular resistance (PVR) of ≥ 3 Wood Units (WU) * No change in pulmonary hypertension medications (eg, ambrisentan, bosentan, macitentan, sildenafil, tadalafil, riociguat) or dosage for at least 90 days prior to Screening * No change in diuretic use or dosage for at least 30 days prior to Screening * Body mass index (BMI) within the range 18.0 - 32.0 kg/m\^2 (inclusive) * Male participants: Male participants and their female partners of childbearing potential must agree to use highly effective contraception from Study Day 1 to at least 90 days after dosing * Female participants: Women of child-bearing potential (WOCPB, defined as premenopausal, not surgically sterile for at least 3 months prior to Screening) must use a highly effective contraception method and agree to be tested for pregnancy from at Screening, Baseline, and 30 days after dosing * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
Exclusion criteria
* Any PH other than idiopathic, hereditary, drug/toxin-induced, or connective tissue disease (CTD) associated PAH (eg, congenital heart disease-associated PAH, portal hypertension-associated PAH, PH belonging to Groups 2 through 5) * Allergy, or documented hypersensitivity or contraindication, to the ingredients of treprostinil palmitil inhalation powder (TPIP) or treprostinil (TRE) * Previous intolerance to prostacyclin analogs or receptor agonists (eg, selexipag) per investigator discretion * History of anaphylaxis or previously documented hypersensitivity reaction to any drug per Investigator discretion * History of heart disease including left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant valvular, constrictive, or atherosclerotic heart disease (myocardial infarction, etc) * Active liver disease or hepatic dysfunction manifested as: 1. Elevated liver function test results (ALT or AST \> 2 × ULN) at Screening 2. Bilirubin \> 1.5 × ULN (isolated bilirubin \> 1.5 × ULN; ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%) at Screening. 3. Known hepatic or biliary abnormalities, not including Gilbert's syndrome or asymptomatic gallstones at Screening. * History of HIV infection/positive HIV serology test result at Screening * History of active/chronic Hepatitis B or C/ positive hepatitis B or C serology test result at Screening * History of abnormal bleeding or bruising * 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 * Active and current symptomatic infection by SARS CoV 2 * Participants with current or recent (past 4 weeks) 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 * Participants receiving triple combination therapy for PAH consisting of endothelin receptor agonists, phosphoesterase type 5 inhibitors, and guanylate cyclase stimulators (riociguat) * Participants receiving prostanoids/prostacyclin agonists * Participants receiving potent CYP2C8 inhibitors, such as gemfibrozil * Have participated in any other interventional clinical studies within 30 days of Baseline * Current or history of substance and/or alcohol abuse * Current user of cigarettes or e-cigarettes * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Experience a Treatment Emergent Adverse Event (TEAE) | Up to 150 days |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Observed Concentration (Cmax) of Treprostinil (TRE) in Plasma | Pre-dose and multiple timepoints post-dose up to Day 2 |
| Time to Maximum Concentration (Tmax) of Treprostinil (TRE) in Plasma | Pre-dose and multiple timepoints post-dose up to Day 2 |
| Change From Baseline in Pulmonary Vascular Resistance (PVR) After TPIP Administration | Day 1: Pre-treatment (Baseline), 8 and 24 hours post-treatment |
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Treprostinil (TRE) in Pasma | Pre-dose and multiple timepoints post-dose up to Day 2 |
| Elimination Half-life (t1/2) of Treprostinil (TRE) in Plasma | Pre-dose and multiple timepoints post-dose up to Day 2 |
| Area Under the Concentration-time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of Treprostinil (TRE) in Plasma | Pre-dose and multiple timepoints post-dose up to Day 2 |
Countries
United States
Participant flow
Recruitment details
The study was terminated by the Sponsor due to low enrolment. As only 1 participant was enrolled in this study, no data is reported here, in order to protect and maintain participant privacy/confidentiality.
Participants by arm
| Arm | Count |
|---|---|
| Treprostinil Palmitil Inhalation Powder (TPIP) Participant received a single dose of TPIP 112.5 μg via oral inhalation on Day 1. The participant then entered into a 16-week EUT Period during which TPIP, administered via oral inhalation, was titrated up to a mean daily dose of 320 μg. | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Race/Ethnicity, Customized American Indian or Alaska Native | — |
| Race/Ethnicity, Customized Asian | — |
| Race/Ethnicity, Customized Black or African American | — |
| Race/Ethnicity, Customized Hispanic or Latino | — |
| Race/Ethnicity, Customized More than one race | — |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | — |
| Race/Ethnicity, Customized Not Hispanic or Latino | — |
| Race/Ethnicity, Customized Unknown or Not Reported | — |
| Race/Ethnicity, Customized White | — |
| Sex/Gender, Customized Female | — |
| Sex/Gender, Customized Male | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Number of Participants Who Experience a Treatment Emergent Adverse Event (TEAE)
Time frame: Up to 150 days
Population: The study was terminated by the Sponsor due to low enrolment. As only 1 participant was enrolled in this study, no data is reported here, in order to protect and maintain participant privacy/confidentiality.
Secondary
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Treprostinil (TRE) in Pasma
Time frame: Pre-dose and multiple timepoints post-dose up to Day 2
Population: The study was terminated by the Sponsor due to low enrolment. As only 1 participant was enrolled in this study, no data is reported here, in order to protect and maintain participant privacy/confidentiality.
Secondary
Area Under the Concentration-time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of Treprostinil (TRE) in Plasma
Time frame: Pre-dose and multiple timepoints post-dose up to Day 2
Population: The study was terminated by the Sponsor due to low enrolment. As only 1 participant was enrolled in this study, no data is reported here, in order to protect and maintain participant privacy/confidentiality.
Secondary
Change From Baseline in Pulmonary Vascular Resistance (PVR) After TPIP Administration
Time frame: Day 1: Pre-treatment (Baseline), 8 and 24 hours post-treatment
Population: The study was terminated by the Sponsor due to low enrolment. As only 1 participant was enrolled in this study, no data is reported here, in order to protect and maintain participant privacy/confidentiality.
Secondary
Elimination Half-life (t1/2) of Treprostinil (TRE) in Plasma
Time frame: Pre-dose and multiple timepoints post-dose up to Day 2
Population: The study was terminated by the Sponsor due to low enrolment. As only 1 participant was enrolled in this study, no data is reported here, in order to protect and maintain participant privacy/confidentiality.
Secondary
Maximum Observed Concentration (Cmax) of Treprostinil (TRE) in Plasma
Time frame: Pre-dose and multiple timepoints post-dose up to Day 2
Population: The study was terminated by the Sponsor due to low enrolment. As only 1 participant was enrolled in this study, no data is reported here, in order to protect and maintain participant privacy/confidentiality.
Secondary
Time to Maximum Concentration (Tmax) of Treprostinil (TRE) in Plasma
Time frame: Pre-dose and multiple timepoints post-dose up to Day 2
Population: The study was terminated by the Sponsor due to low enrolment. As only 1 participant was enrolled in this study, no data is reported here, in order to protect and maintain participant privacy/confidentiality.