Primary Pulmonary HypertensionPhase 3INSPIRENCT03399604
Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil
A Phase 3 study testing LIQ861 Inhaled Treprostinil in people with Primary Pulmonary Hypertension, run by Liquidia Technologies, Inc. at 38 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Pulmonary Hypertension
- What is being tested?
- LIQ861 Inhaled Treprostinil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 38 sitesUnited States
- Study dates
- 2 Jan 2018to 25 Nov 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
Show all 25Show fewer
- 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).
Trial locations and contacts
38 sites in 1 country.
38 sites in 1 country
United States38 sites
University of New Mexico Health Science Center
Albuquerque, New Mexico, 87106
Emory University School of Medicine
Atlanta, Georgia, 30322
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Tufts Medical Center
Boston, Massachusetts, 02111
University of North Carolina School of Medicine
Chapel Hill, North Carolina, 27599
Northwestern Medicine, Feinberg School of Medicine
Chicago, Illinois, 60611
University of Chicago Medicine
Chicago, Illinois, 60637
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267
University Hospitals of Cleveland Medical Center
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
the Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
UT Southwestern Medical Center
Dallas, Texas, 75390
INOVA Fairfax Medical Campus
Falls Church, Virginia, 22042
University of Florida
Gainesville, Florida, 32610
Houston Methodist Lung Center
Houston, Texas, 77030
University of Texas - Health Science Center
Houston, Texas, 77030
Mayo Clinic-Jacksonville
Jacksonville, Florida, 32224
University of Kansas Medical Center
Kansas City, Kansas, 66103
West Los Angeles VA Healthcare Center
Los Angeles, California, 90073
Kentuckiana Pulmonary Research Center
Louisville, Kentucky, 40202
Wellstar Research Institute
Marietta, Georgia, 30060
The Medical College of Wisconsin/Froedtert Hospital
Milwaukee, Wisconsin, 53226
NYU Winthrop University Hospital
Mineola, New York, 11501
University of Minnesota
Minneapolis, Minnesota, 55435
Ochsner Medical Center
New Orleans, Louisiana, 70121
NYU Langone Health
New York, New York, 10279
AdventHealth
Orlando, Florida, 32803
University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104
Banner University Medical Center
Phoenix, Arizona, 85006
Arizona Pulmonary Specialists, Ltd.
Phoenix, Arizona, 85012
Alleghany General Hospital
Pittsburgh, Pennsylvania, 15212
UPMC Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213
Oregon Health and Science Center
Portland, Oregon, 97239
Mayo Clinic-Rochester
Rochester, Minnesota, 55905
UC Davis Medical Center
Sacramento, California, 95817
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Washington University School of Medicine
St Louis, Missouri, 63110
Los Angeles Biomedical Research Center
Torrance, California, 90502
About this study
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
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).
Read the 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
- Being tested
- LIQ861 Inhaled Treprostinil
- Keywords
- Pulmonary Arterial Hypertension, Idiopathic Pulmonary Arterial Hypertension, Heritable Pulmonary Arterial Hypertension, Drug Induced Pulmonary Arterial Hypertension, Toxin Induced Pulmonary Arterial Hypertension, Connective tissue disease
- Medical subject headings
- Familial Primary Pulmonary Hypertension, Pulmonary Arterial Hypertension, Connective Tissue Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LIQ861 Inhaled TreprostinilDrug
Also called inhaled treprostinil, inhaled prostacyclin
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.
| Study group | Role | What they receive |
|---|---|---|
| LIQ861 Inhaled Treprostinil | Experimental | 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. Receives: Drug: LIQ861 Inhaled Treprostinil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
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
Measured: Baseline, Week 2, Month 1, Month 2 Visits, with bimonthly follow up for up to 16 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2018
- Study start2 Jan 2018
- Primary completion6 May 2019
- Study completion25 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study will evaluate the long term safety and tolerability of LIQ861 in PAH patients transitioning from stable doses of inhaled treprostinil therapy, or who are taking no more than 2 approved, non-prostacylcin, oral PAH therapies. Patients transitioning from inhaled treprostinil will be initiated at a comparable dose of LIQ861, and then titrate in 25ug incremental doses to tolerance and symptom relief. Patients adding LIQ861 to current oral therapies will start at a 25ug dose, and increase in 25ug increments on a weekly basis to tolerance and symptom relief. A subset of the patients transitioning from inhaled treprostinil will be enrolled in a one-directional crossover to compare the bioavailability and pharmacokinetics of treprostinil as they transition to LIQ861. Serial PK sample collections will be taken on back to back days for transitioning and LIQ861 treprostinil formulations. These patients will then continue to be followed as all other patients enrolled in the study.
- Masking
- None (open label)
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liquidia Technologies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Nuventra, Inc.
- Responsible party
- Sponsor
- Investigators
- Nicholas S Hill, MD, Principal investigator, Tufts Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03399604
- Sponsor's protocol ID
- LTI-301
- Acronym
- INSPIRE
- Status last verified
- Jul 2024
- First submitted
- 3 Jan 2018
- Last updated
- 30 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33282202
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03399604
- Acronym / sponsor ID
- INSPIRE / LTI-301
- Conditions
- Primary Pulmonary Hypertension
- Keywords
- Pulmonary Arterial Hypertension, Idiopathic Pulmonary Arterial Hypertension, Heritable Pulmonary Arterial Hypertension, Drug Induced Pulmonary Arterial Hypertension, Toxin Induced Pulmonary Arterial Hypertension, Connective tissue disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Liquidia Technologies, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Nuventra, Inc.
- Study start
- 2 Jan 2018 (actual)
- Primary completion
- 6 May 2019 (actual)
- Study completion
- 25 Nov 2019 (actual)
- First posted
- 16 Jan 2018 (actual)
- Results
- Posted 30 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study will evaluate the long term safety and tolerability of LIQ861 in PAH patients transitioning from stable doses of inhaled treprostinil therapy, or who are taking no more than 2 approved, non-prostacylcin, oral PAH therapies. Patients transitioning from inhaled treprostinil will be initiated at a comparable dose of LIQ861, and then titrate in 25ug incremental doses to tolerance and symptom relief. Patients adding LIQ861 to current oral therapies will start at a 25ug dose, and increase in 25ug increments on a weekly basis to tolerance and symptom relief. A subset of the patients transitioning from inhaled treprostinil will be enrolled in a one-directional crossover to compare the bioavailability and pharmacokinetics of treprostinil as they transition to LIQ861. Serial PK sample collections will be taken on back to back days for transitioning and LIQ861 treprostinil formulations. These patients will then continue to be followed as all other patients enrolled in the study.
| Arm | Type | Receives |
|---|---|---|
| LIQ861 Inhaled Treprostinil | Experimental | Drug: LIQ861 Inhaled TreprostinilLIQ861 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- The patient has been diagnosed with PAH and is NYHA Functional Class II - IV at Screening.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LIQ861 Inhaled TreprostinilAlso: inhaled treprostinil, inhaled prostacyclinLIQ861 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. | Drug | LIQ861 Inhaled Treprostinil |
Primary outcome
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33282202Roscigno 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicholas S Hill, MD principal investigator
Tufts Medical Center
38 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LIQ861 Inhaled Treprostinil in people with Primary Pulmonary Hypertension, run by Liquidia Technologies, Inc. at 38 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events (time frame: Baseline, Week 2, Month 1, Month 2 Visits, with bimonthly follow up for up to 16 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03399604, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2024.