Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil

Primary Pulmonary Hypertension Clinical Trial

— INSPIRE  

Official title:

A Phase 3 Open-label, Multicenter Study to Evaluate the Long-term Safety and Tolerability of Inhaled LIQ861(Treprostinil) in Pulmonary Arterial Hypertension (WHO Group 1) Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03399604
• Other study ID #: LTI-301
• Status: Completed
• Phase: Phase 3
• Start date: January 2, 2018
• Est. completion date: November 25, 2019

Study information

• Verified date: November 2020
• Source: Liquidia Technologies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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). A secondary objective of this study is to evaluate the comparative bioavailability of treprostinil between two formulations of inhaled therapy.

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 information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: November 25, 2019
• Est. primary completion date: May 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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:

1. Idiopathic PAH (1.1), or

2. Heritable PAH (1.2), or

3. Drug and toxin induced PAH (1.3), or

4. 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.

1. 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

2. 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.

Exclusion Criteria:

• 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).

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary
• Primary Pulmonary Hypertension

Intervention

Drug:
• LIQ861 Inhaled Treprostinil
LIQ861 bulk powder is generated from a treprostinil/excipient matrix from which particles of precise size and shape are created and filled into a hydroxypropyl methylcellulose (HPMC) capsule (size 3). LIQ861 capsules are provided in capsule strengths of 25 µg, 50 µg, 75 µg and 100 µg treprostinil.

Locations

Country	Name	City	State
United States	University of New Mexico Health Science Center	Albuquerque	New Mexico
United States	Emory University School of Medicine	Atlanta	Georgia
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of North Carolina School of Medicine	Chapel Hill	North Carolina
United States	Northwestern Medicine, Feinberg School of Medicine	Chicago	Illinois
United States	University of Chicago Medicine	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals of Cleveland Medical Center	Cleveland	Ohio
United States	the Ohio State University Wexner Medical Center	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	INOVA Fairfax Medical Campus	Falls Church	Virginia
United States	University of Florida	Gainesville	Florida
United States	Houston Methodist Lung Center	Houston	Texas
United States	University of Texas - Health Science Center	Houston	Texas
United States	Mayo Clinic-Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	West Los Angeles VA Healthcare Center	Los Angeles	California
United States	Kentuckiana Pulmonary Research Center	Louisville	Kentucky
United States	Wellstar Research Institute	Marietta	Georgia
United States	The Medical College of Wisconsin/Froedtert Hospital	Milwaukee	Wisconsin
United States	NYU Winthrop University Hospital	Mineola	New York
United States	University of Minnesota	Minneapolis	Minnesota
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	NYU Langone Health	New York	New York
United States	AdventHealth	Orlando	Florida
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists, Ltd.	Phoenix	Arizona
United States	Banner University Medical Center	Phoenix	Arizona
United States	Alleghany General Hospital	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	Oregon Health and Science Center	Portland	Oregon
United States	Mayo Clinic-Rochester	Rochester	Minnesota
United States	UC Davis Medical Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Los Angeles Biomedical Research Center	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
Liquidia Technologies, Inc.	Nuventra, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events and Serious 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	Baseline, Week 2, Month 1, Month 2 Visits, with bimonthly follow up for up to 30 months.