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

NCT ID: NCT03399604

Last Updated: 2024-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-02
• Study Completion Date: 2019-11-25

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).

Conditions

Primary Pulmonary Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

LIQ861 Inhaled Treprostinil

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

inhaled treprostinil; inhaled prostacyclin

Eligibility Criteria

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.

• 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).

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.

• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nuventra, Inc.

INDUSTRY

Sponsor Role: collaborator

Liquidia Technologies, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicholas S Hill, MD

Role: PRINCIPAL_INVESTIGATOR

Tufts Medical Center

Locations

Banner University Medical Center

Phoenix, Arizona, United States

Arizona Pulmonary Specialists, Ltd.

Phoenix, Arizona, United States

West Los Angeles VA Healthcare Center

Los Angeles, California, United States

UC Davis Medical Center

Sacramento, California, United States

Los Angeles Biomedical Research Center

Torrance, California, United States

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

University of Florida

Gainesville, Florida, United States

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States

AdventHealth

Orlando, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Wellstar Research Institute

Marietta, Georgia, United States

Northwestern Medicine, Feinberg School of Medicine

Chicago, Illinois, United States

University of Chicago Medicine

Chicago, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Kentuckiana Pulmonary Research Center

Louisville, Kentucky, United States

Ochsner Medical Center

New Orleans, Louisiana, United States

Tufts Medical Center

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic-Rochester

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of New Mexico Health Science Center

Albuquerque, New Mexico, United States

NYU Winthrop University Hospital

Mineola, New York, United States

NYU Langone Health

New York, New York, United States

University of North Carolina School of Medicine

Chapel Hill, North Carolina, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

University Hospitals of Cleveland Medical Center

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

the Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Oregon Health and Science Center

Portland, Oregon, United States

University of Pennsylvania Health System

Philadelphia, Pennsylvania, United States

Alleghany General Hospital

Pittsburgh, Pennsylvania, United States

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Houston Methodist Lung Center

Houston, Texas, United States

University of Texas - Health Science Center

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

INOVA Fairfax Medical Campus

Falls Church, Virginia, United States

The Medical College of Wisconsin/Froedtert Hospital

Milwaukee, Wisconsin, United States

Countries

United States

References

Roscigno R, Vaughn T, Anderson S, Wargin W, Hunt T, Hill NS. Pharmacokinetics and tolerability of LIQ861, a novel dry-powder formulation of treprostinil. Pulm Circ. 2020 Nov 19;10(4):2045894020971509. doi: 10.1177/2045894020971509. eCollection 2020 Oct-Dec.

Reference Type: DERIVED

PMID: 33282202 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

LTI-301

Identifier Type: -

Identifier Source: org_study_id