Clinical trial NCT03950739: Open-label, Clinical Study to Evaluate the Safety and Tolerability of TreT in Subjects With PAH Currently Using Tyvaso
Official title: An Open-label, Clinical Study to Evaluate the Safety and Tolerability of Treprostinil Inhalation Powder (TreT) in Subjects With Pulmonary Arterial Hypertension Currently Using Tyvaso
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Arterial Hypertension
Keywords: prostacyclin
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-05-15
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-sequence in which subjects on a stable regimen of Tyvaso switched to a corresponding dose of TreT
Primary purpose: TREATMENT

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.

Detailed description: United Therapeutics Corporation (UTC) developed a combination drug-device product comprised of a dry powder formulation of Treprostinil Inhalation Powder (TreT) and a small, portable, dry powder inhaler. In this Phase 1b safety and tolerability study, patients with PAH on a stable dose of Tyvaso (6 to 12 breaths 4 times daily \[QID\]) were evaluated after switching to a corresponding dose of TreT. Patients underwent PK assessments, safety assessments, a 6-Minute Walk Test (6MWT), and questionnaires for satisfaction/preference for inhaled devices and patient-reported PAH symptoms and impact. Following 3 weeks of treatment with TreT, patients were offered the opportunity to participate in the Optional Extension Phase until the drug/device became commercially available.

Eligibility criteria: Inclusion Criteria:

1. Subject voluntarily gave informed consent to participate in the study.
2. Subject was aged 18 years or older at the time of signing informed consent.
3. 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:

   1. Abstained from intercourse (when it was in line with their preferred and usual lifestyle), or
   2. 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.
4. 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.
5. Subject was diagnosed with PAH as defined by the following World Health Organization (WHO) Group 1 categories:

   1. Idiopathic/familial
   2. Associated with unrepaired or repaired congenital systemic-to-pulmonary shunts (repaired ≥5 years prior to Screening)
   3. Associated with collagen vascular disease
   4. Associated with human immunodeficiency virus
   5. Associated with appetite suppressant/other drug or toxin use
6. 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).
7. Baseline 6MWD ≥150 m.
8. 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.
9. The subject had evidence of forced expiratory volume in 1 second (FEV1) ≥60% and FEV1/forced vital capacity ratio ≥60% during the 6 months prior to enrollment.
10. In the opinion of the Investigator, the subject was able to communicate effectively with study personnel, and was considered reliable, willing, and likely to be cooperative with protocol requirements, including all study visits.

Exclusion Criteria:

1. Subject was pregnant or lactating.
2. Subject was diagnosed with pulmonary hypertension for reasons other than WHO Group 1 as outlined in Inclusion Criterion 5 (including but not limited to portal hypertension, chronic thromboembolic disease, pulmonary veno-occlusive disease, hemolytic anemia, sarcoidosis).
3. 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).
4. 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.
5. Subject experienced an acute exacerbation of disease or hospitalization for any reason within 30 days of the Screening Visit or between Screening and Baseline.
6. Subject was WHO Functional Class IV at Screening.
7. 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.
8. Subject had a history of anaphylaxis, a documented hypersensitivity reaction, or a clinically significant idiosyncratic reaction to treprostinil or excipients in the investigational product.
9. Subject had conditions that, in the opinion of the Investigator, would make the subject ineligible.
10. Subject was not able to perform inhalation maneuvers that met inspiratory training criteria.
11. 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.
12. 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.
13. Initiation of pulmonary rehabilitation within 12 weeks prior to the Baseline Visit.

Primary outcomes:
measure: Change in 6-Minute Walk Distance (6MWD) From Baseline to Week 3
timeFrame: From Baseline to 3 weeks of treatment with TreT
measure: Subject Satisfaction With and Preference for Inhaled Treprostinil Devices
timeFrame: After 3 weeks of treatment with TreT (after switching from the Tyvaso Inhalation System)
measure: Change in Patient-reported PAH Symptoms and Impact From Baseline to Week 3
timeFrame: From Baseline to 3 weeks of treatment with TreT
measure: Change in Patient-reported PAH Symptoms and Impact From Baseline to Week 11 (for Subjects Participating in the OEP)
timeFrame: From Baseline to 11 weeks of treatment with TreT
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Department of Veterans Affairs Greater Los Angeles Healthcare System
state: California
city: Jacksonville
country: United States
facility: Ascension / St. Vincent's Lung Institute
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida Center for Advanced Lung Disease
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville Clinical Trials Unit
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center Division of Cardiology
state: Maryland
city: Philadelphia
country: United States
facility: Penn Medicine University City
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond, Inc.
state: Virginia
Study officials:
References:
citation: 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.