Open-label, Clinical Study to Evaluate the Safety and Tolerability of TreT in Subjects With PAH Currently Using Tyvaso

NCT03950739 | Completed Phase 1 Results FDA Drug

• 1 other identifier: TIP-PH-101
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 16

Brief Summary

This was a Phase 1b safety and tolerability single-sequence study in which PAH subjects on a stable regimen of Tyvaso switched to a corresponding dose of TreT.

Conditions

Pulmonary Arterial Hypertension

Keywords

prostacyclin

Outcome Measures

Primary Outcomes (4)

• Change in 6-Minute Walk Distance (6MWD) From Baseline to Week 3

  6MWD was evaluated at study entry and after 3 weeks of treatment with TreT.

  From Baseline to 3 weeks of treatment with TreT

• Subject Satisfaction With and Preference for Inhaled Treprostinil Devices

  Subject satisfaction with and preference for the inhaled treprostinil device was evaluated with the Preference Questionnaire for Inhaled Treprostinil Devices (PQ-ITD). The PQ-ITD is a questionnaire given to evaluate subject satisfaction with and preference for inhaled treprostinil devices. The questionnaire provides 12 different statements around inhaled device satisfaction and allows for 5 response options: strongly disagree, disagree, neutral, agree, and strongly agree.

  After 3 weeks of treatment with TreT (after switching from the Tyvaso Inhalation System)

• Change in Patient-reported PAH Symptoms and Impact From Baseline to Week 3

  Patient-reported PAH symptoms and impact were evaluated with the PAH Symptoms and Impact (PAH-SYMPACT) Questionnaire. The PAH-SYMPACT is a 23-item patient-reported outcome questionnaire that consists of 11 symptom items, 11 impact items, and 1 item on oxygen use. The symptom items are divided into cardiopulmonary and cardiovascular domains, and the impact items are divided into physical and emotional/cognitive domains. Symptom and impact domain scores (range 0 to 4) are calculated as the sum of the scores for the items included in the domain divided by the number of items in the domain. For all domains, a higher score indicates more severe symptoms/impacts.

  From Baseline to 3 weeks of treatment with TreT

• Change in Patient-reported PAH Symptoms and Impact From Baseline to Week 11 (for Subjects Participating in the OEP)

  Patient-reported PAH symptoms and impact were evaluated with the PAH Symptoms and Impact (PAH-SYMPACT) Questionnaire. The PAH-SYMPACT is a 23-item patient-reported outcome questionnaire that consists of 11 symptom items, 11 impact items, and 1 item on oxygen use. The symptom items are divided into cardiopulmonary and cardiovascular domains, and the impact items are divided into physical and emotional/cognitive domains. Symptom and impact domain scores (range 0 to 4) are calculated as the sum of the scores for the items included in the domain divided by the number of items in the domain. For all domains, a higher score indicates more severe symptoms/impacts.

  From Baseline to 11 weeks of treatment with TreT

Study Arms (1)

Tyvaso to TreT

EXPERIMENTAL

Each subject received a corresponding dose of TreT for 3 weeks during the Treatment Phase based on the subject's current stable Tyvaso dose.

Drug: Treprostinil Inhalation Powder

Interventions

Treprostinil Inhalation Powder DRUG

Treprostinil inhalation powder single-use cartridges containing either 32 or 48 micrograms of treprostinil per cartridge (QID)

Also known as: TreT

Tyvaso to TreT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject voluntarily gave informed consent to participate in the study.
• Subject was aged 18 years or older at the time of signing informed consent.
• Women of childbearing potential were those who had experienced menarche and who had not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or were not postmenopausal (defined as amenorrhea for at least 12 consecutive months). WOCBP must have been nonpregnant (as confirmed by a urine pregnancy test at Screening prior to initiating study medication), nonlactating, and did 1 of the following:
• Abstained from intercourse (when it was in line with their preferred and usual lifestyle), or
• Used 2 medically acceptable, highly effective forms of contraception for the duration of study, and at least 30 days after discontinuing TreT. Medically acceptable, highly effective forms of contraception included approved hormonal contraceptives (oral, injectable, and implantable), intrauterine devices or systems, and barrier methods (such as a condom or diaphragm) when used with a spermicide.
• Males with a partner of childbearing potential must have used a condom for the duration of treatment and for at least 48 hours after discontinuing TreT.
• Subject was diagnosed with PAH as defined by the following World Health Organization (WHO) Group 1 categories:
• Idiopathic/familial
• Associated with unrepaired or repaired congenital systemic-to-pulmonary shunts (repaired ≥5 years prior to Screening)
• Associated with collagen vascular disease
• Associated with human immunodeficiency virus
• Associated with appetite suppressant/other drug or toxin use
• Subject must have started Tyvaso ≥3 months prior to the Baseline Visit and was currently on a stable regimen (no change in dose within 30 days of Baseline Visit) of Tyvaso (6 to 12 breaths QID).
• Baseline 6MWD ≥150 m.
• If the subject was currently receiving other approved background therapy (eg, endothelin receptor antagonist or phosphodiesterase type 5 inhibitor or both), the subject must have been on a stable dose with no additions or discontinuations for a minimum of 30 days prior to Screening.

You may not qualify if:

• Subject was pregnant or lactating.
• Subject had a history of uncontrolled sleep apnea, parenchymal lung disease, or 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).
• Subject was currently taking any other prostacyclin analogue or agonist, including but not limited to selexipag, epoprostenol, iloprost, or beraprost; except for acute vasoreactivity testing.
• Subject experienced an acute exacerbation of disease or hospitalization for any reason within 30 days of the Screening Visit or between Screening and Baseline.
• Subject was WHO Functional Class IV at Screening.
• Subject had used any investigational drug/device or participated in any other investigational study with therapeutic intent within 30 days prior to the Screening Visit.
• Subject had a history of anaphylaxis, a documented hypersensitivity reaction, or a clinically significant idiosyncratic reaction to treprostinil or excipients in the investigational product.
• Subject had conditions that, in the opinion of the Investigator, would make the subject ineligible.
• Subject was not able to perform inhalation maneuvers that met inspiratory training criteria.
• Subject had a musculoskeletal disorder (eg, arthritis affecting the lower limbs, recent hip or knee joint replacement) or any disease that would likely be the primary limit to ambulation, or was connected to a machine that was not portable enough to allow for a 6MWT.
• Subject had a new type of chronic therapy (including but not limited to oxygen, a different class of vasodilator, diuretic, and digoxin) for pulmonary hypertension added within 30 days of the Screening Phase.
• Initiation of pulmonary rehabilitation within 12 weeks prior to the Baseline Visit.

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (16)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Department of Veterans Affairs Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

Ascension / St. Vincent's Lung Institute

Jacksonville, Florida, 32204, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of South Florida Center for Advanced Lung Disease

Tampa, Florida, 33606, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Louisville Clinical Trials Unit

Louisville, Kentucky, 40202, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

University of Maryland Medical Center Division of Cardiology

Baltimore, Maryland, 21201, United States

Location

Penn Medicine University City

Philadelphia, Pennsylvania, 19104, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

Pulmonary Associates of Richmond, Inc.

Richmond, Virginia, 23230, United States

Location

Related Publications (2)

• Sahay S, Palevsky H, El-Kersh K, Restrepo-Jaramillo R, Bajwa AA, Desai S, Joly JM, Spikes LA, Eggert MS, Johri S, Shapiro SM, Fisher MR, Shah TG, Ramani GV, Mehta JP, Thrasher CM, Deng C, Smith P, Broderick M, Burger CD. BREEZE Optional Extension Phase: Long-term safety and efficacy of treprostinil dry powder inhaler (Tyvaso DPI) in pulmonary arterial hypertension. Respir Med. 2025 Nov;248:108318. doi: 10.1016/j.rmed.2025.108318. Epub 2025 Aug 27.

  PMID: 40882760 DERIVED

• Spikes LA, Bajwa AA, Burger CD, Desai SV, Eggert MS, El-Kersh KA, Fisher MR, Johri S, Joly JM, Mehta J, Palevsky HI, Ramani GV, Restrepo-Jaramillo R, Sahay S, Shah TG, Deng C, Miceli M, Smith P, Shapiro SM. BREEZE: Open-label clinical study to evaluate the safety and tolerability of treprostinil inhalation powder as Tyvaso DPI in patients with pulmonary arterial hypertension. Pulm Circ. 2022 Apr 7;12(2):e12063. doi: 10.1002/pul2.12063. eCollection 2022 Apr.

  PMID: 35514770 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: United Therapeutics Global Medical Information
• Organization: United Therapeutics Corp.

clinicaltrials@unither.com

919-485-8350

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-sequence in which subjects on a stable regimen of Tyvaso switched to a corresponding dose of TreT

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: May 15, 2019
• Study Start: September 17, 2019
• Primary Completion: August 22, 2023
• Study Completion: August 22, 2023
• Last Updated: November 1, 2024
• Results First Posted: November 1, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)