Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil
- Conditions
- Primary Pulmonary Hypertension
- Interventions
- Drug: LIQ861 Inhaled Treprostinil
- Registration Number
- NCT03399604
- Lead Sponsor
- Liquidia Technologies, Inc.
- Brief Summary
The primary objective of this study is to evaluate the long-term safety and tolerability of LIQ861, a dry powder formulation of treprostinil, in patients with Pulmonary Arterial Hypertension (PAH).
- Detailed Description
One of the greatest impediments to patient treatment satisfaction with current inhaled treprostinil therapy is inconvenience. Currently, PAH patients using inhaled treprostinil may require more than 36 breaths per day using a nebulizer requiring daily set up and cleaning. The use of a discrete, hand-held dry powder inhaler to deliver treprostinil to the lungs could represent a major improvement in convenience and patient satisfaction, thereby improving the quality of life for PAH patients. Liquidia is pursuing approval of LIQ861, an inhalation dry powder formulation of treprostinil that is produced using Liquidia's PRINT® Technology (Particle Replication in Nonwetting Templates), as an alternative to current inhaled treprostinil therapy for the treatment of patients with PAH (WHO Group 1).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 121
-
signed informed consent by patient prior to study enrollment
-
18 years of age or older
-
If female of childbearing potential, a negative pregnancy test at the Baseline Visit and agrees to practice adequate birth control throughout the duration of the study. If the patient is postmenopausal or has documented surgical sterilization, a pregnancy test and birth control is not necessary.
-
The patient has been diagnosed with PAH belonging to the following subgroups of the updated Nice Clinical Classification Group 1 (Simonneau, Gatzoulis et al. 2013), which include:
- Idiopathic PAH (1.1), or
- Heritable PAH (1.2), or
- Drug and toxin induced PAH (1.3), or
- PAH associated with connective tissue disease (1.4.1), HIV infection (1.4.2), or congenital heart disease (1.4.4) with simple systemic-to-pulmonary shunt at least 1 year after surgical repair
-
The patient has been diagnosed with PAH and is NYHA Functional Class II - IV at Screening.
- has documented stable doses of approved inhaled therapy for at least 3 months prior to screening and is willing and able to transition from their prescribed dose of inhaled therapy to study drug, or
- has documented stable doses of no more than two approved oral therapies for at least 3 months prior to screening and is willing and able to add LIQ861 to their treatment regimen.
-
The patient can complete a baseline six-minute walk distance (6MWD) ≥ 150 m.
-
The patient has had evidence of FEV1 ≥ 60% and FEV1/FVC ratio ≥ 60% during the 6-month period prior to enrollment.
- The patient's clinical condition is such that, in the opinion of the Investigator, they are not expected to remain clinically stable for the duration of the study.
- Patients with PH in the Updated Nice Classification Groups 2-5, or PAH Group 1 subgroups not covered by the inclusion criteria (e.g., associated with portal hypertension [1.4.3] or with schistosomiasis [1.4.5]).
- The patient is currently taking oral prostacyclin analogues or agonists, including treprostinil and selexipag.
- The patient has had any PAH medication (except for anticoagulants) discontinued within 14 days of Baseline.
- The patient has had a new type of chronic therapy (including but not limited to oxygen, a different class of vasodilator, diuretic, digoxin, and digitalis) for pulmonary hypertension added within 30 days of Baseline.
- The patient has uncontrolled systemic hypertension as evidenced by persistent systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg.
- The patient has a history of hemodynamically significant left-sided heart disease including, but not limited to: aortic or mitral valve disease, pericardial constriction, restrictive or congestive cardiomyopathy, or coronary artery disease (CAD).
- The patient has had an atrial septostomy.
- The patient has any serious or life-threatening disease other than conditions associated with PAH (e.g. malignancy requiring aggressive chemotherapy, end stage renal disease, etc.).
- The patient is taking any excluded medications listed in the Investigator's Brochure, namely inhibitors and inducers of CYP2C8
- The patient has a hypersensitivity or allergy to any of the ingredients of LIQ861 or other clinically relevant allergies (clinical relevance per Investigator judgment).
- The patient has had a pulmonary infarction (defined as infarction in more than one lung segment documented by V/Q scan or pulmonary angiography) within two weeks of Screening.
- The patient has had a stroke or transient ischemic attack (TIA) within six months of Screening.
- The patient has evidence of an active uncontrolled sepsis or systemic infection during Screening.
- The patient is pregnant or lactating.
- The patient has any musculoskeletal disease or any other disease that would limit ambulation.
- The patient has participated in an investigational product or device study within the 30 days prior to Screening.
- The patient has current evidence of drug abuse in the opinion of the Investigator.
- The patient has severe hepatic impairment as evidenced by any history of ascites AND encephalopathy.
- The patient has severe renal impairment (eGFR < 35).
- The patient is taking inhaled treprostinil doses of greater than 90 μg (more than 15 breaths).
Additional Exclusion Criteria for PK Sub-Study:
- The patient meets any of Primary Exclusion Criteria #1 - 19.
- The patient has moderate or severe renal impairment (eGFR < 60).
- The patient is taking inhaled treprostinil doses of greater than 72 μg (more than 12 breaths).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LIQ861 Inhaled Treprostinil LIQ861 Inhaled Treprostinil LIQ861 inhaled treprostinil at capsule strengths of 25 μg, 50 μg, 75 μg and 100 μg. LIQ861 will be administered using the RS00 Model 8 dry powder inhalation (DPI) device (Plastiape S.p.A.; Osnago, Italy) at dose levels of 25 μg to 150 μg treprostinil QID in individual patients.
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events Baseline, Week 2, Month 1, Month 2 Visits, with bimonthly follow up for up to 16 months. There were two treatment arms analyzed for events in the study. All subjects that participated in the PK study were part of the transition group and not analyzed separately for adverse events.
Treatment-Emergent Adverse Events and Serious Adverse Events will be grouped by MedDRA System Organ Class, dose level, time on drug, and relationship to dose titration
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (38)
West Los Angeles VA Healthcare Center
🇺🇸Los Angeles, California, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Los Angeles Biomedical Research Center
🇺🇸Torrance, California, United States
University of Pennsylvania Health System
🇺🇸Philadelphia, Pennsylvania, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
the Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Northwestern Medicine, Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
University of Texas - Health Science Center
🇺🇸Houston, Texas, United States
Wellstar Research Institute
🇺🇸Marietta, Georgia, United States
University of Chicago Medicine
🇺🇸Chicago, Illinois, United States
INOVA Fairfax Medical Campus
🇺🇸Falls Church, Virginia, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic-Rochester
🇺🇸Rochester, Minnesota, United States
Oregon Health and Science Center
🇺🇸Portland, Oregon, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
The Medical College of Wisconsin/Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
University of Colorado Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Banner University Medical Center
🇺🇸Phoenix, Arizona, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Arizona Pulmonary Specialists, Ltd.
🇺🇸Phoenix, Arizona, United States
Mayo Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
NYU Langone Health
🇺🇸New York, New York, United States
NYU Winthrop University Hospital
🇺🇸Mineola, New York, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University Hospitals of Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of North Carolina School of Medicine
🇺🇸Chapel Hill, North Carolina, United States
Houston Methodist Lung Center
🇺🇸Houston, Texas, United States
University of New Mexico Health Science Center
🇺🇸Albuquerque, New Mexico, United States
Alleghany General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Presbyterian Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
AdventHealth
🇺🇸Orlando, Florida, United States
Kentuckiana Pulmonary Research Center
🇺🇸Louisville, Kentucky, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States