2023-505541-99-00
Completed
Phase 2
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
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Insmed Inc.
- Enrollment
- 23
- Locations
- 23
- Primary Endpoint
- Change from Baseline in PVR at Week 16
Overview
Brief Summary
To assess the effect of Treprostinil Palmitil Inhalation Powder (TPIP) compared with placebo on Pulmonary Vascular Resistance (PVR)
Study Design
- Allocation
- Not Applicable
- Primary Purpose
- 4-week Follow-up Period
- Masking
- None
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Participants must be ≥ 18 to ≤ 75 years at the time of signing the ICF
- •At least two 6MWTs during Screening with a 6MWT distance between 150 and 450 meters in length where both values are within 15% of each other.
- •Right heart catheterization at Screening (or within 30 days prior to Screening, if available) with all the following hemodynamic findings: • Mean PAP ? 25 mmHg at rest • PCWP ? 15 mmHg • PVR of ? 5 WU"
- •BMI within the range 18.0-37.0 kg/m2 (inclusive).
- •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 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. Such methods include true abstinence (refraining from heterosexual intercourse during the study), combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems. • 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-oopherectomy), 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. Such methods include true abstinence (refraining from heterosexual intercourse during the study), combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation and supplemented with a double barrier (preferably male condom), intrauterine devices, intrauterine hormone-releasing systems, or vasectomized partner. For WOCBBP ≤45 years, an additional confirmatory testing of FSH level with a threshold of >40 mIU/mL should be performed to be considered infertile. All WOCBP must have a negative urine pregnancy test prior to randomization."
- •Female participants of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline.
- •Male participants with pregnant or non-pregnant WOCBP partner must use a condom in order to avoid potential exposure to embryo/fetus.
- •Capable of giving signed informed consent
- •Able to understand and comply with protocol requirements
- •Participants must have a diagnosis of WHO Group 1 PH (PAH) in any of the following subtypes: • idiopathic; • heritable or • drug/toxininduced or CTD-associated PAH • Congenital heart disease-related with simple systemic-to-pulmonary shunt at least 1 year following repair
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 hypertensionassociated PAH, PH belonging to Groups 2 through 5).
- •Acutely decompensated heart failure within 30 days of Screening Visit.
- •Abnormal renal function (estimated glomerular filtration rate < 30 mL/min/1.73m2) at Screening.
- •Active liver disease or hepatic dysfunction manifested as: in • Elevated liver function test results (ALT or AST > 2 × ULN) • Bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN; ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%) • Known hepatic or biliary abnormalities, not including Gilbert's syndrome or asymptomatic gallstones"
- •History of HIV infection
- •Established diagnosis of hepatitis B viral infection, or positive for HBsAg at the time of Screening. • Participants who have gained immunity for hepatitis B virus infection after vaccination are eligible for the study. • Participants with positive HBcAbs are eligible for the study only if the hepatitis B virus DNA level is undetectable."
- •Established diagnosis of hepatitis C viral infection at the time of screening. Participants positive for hepatitis C antibody are eligible for the study only if hepatitis C virus RNA is negative.
- •Active and current symptomatic 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.
Outcomes
Primary Outcomes
Change from Baseline in PVR at Week 16
Change from Baseline in PVR at Week 16
Secondary Outcomes
- Change from Baseline in 6MWT distance at Week 5, Week 10, and Week 16
- Percent change from Baseline in 6MWT distance at Week 5, Week 10 and Week 16
- Frequency of AEs and changes from Baseline in clinical laboratory evaluations, vital signs, ECG, and physical examination over the 16-week treatment period
- Plasma PK parameters of TP and TRE, including Cmax, tmax, AUC24, AUC∞, AUClast, CL/F, Vd/F, and t½, on Day 1 and at Week 10
- Change from Baseline in the concentration of NT-proBNP at Week 5, Week 10 and Week 16
Investigators
Fraz Ismat
Scientific
Insmed Inc.
Study Sites (23)
Loading locations...
Similar Trials
Completed
Phase 2
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Arterial HypertensionPulmonary Arterial HypertensionNCT05147805Insmed Incorporated102
Completed
Phase 1
Treatment of Pulmonary Hypertension Associated COPD With Inhaled Treprostinil-1Pulmonary HypertensionCOPDNCT01758744University of Colorado, Denver10
Terminated
Phase 3
A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Participants With Pulmonary Hypertension (PH) Due to Chronic Obstructive Pulmonary Disease (COPD)Pulmonary HypertensionChronic Obstructive Pulmonary DiseaseNCT03496623United Therapeutics188
Completed
Phase 3
Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary FibrosisIdiopathic Pulmonary FibrosisInterstitial Lung DiseaseNCT04708782United Therapeutics598
Withdrawn
Phase 3
Inhaled Treprostinil for PAH: Open-label ExtensionPulmonary Arterial HypertensionNCT01557660United Therapeutics