Purpose

This is a multicenter, randomized, double-blind, placebo-controlled, 30-week, adaptive cross-over study, with a Treatment Period of approximately 26 weeks under the Original Design or, if applicable, a 17-week parallel study, with a Treatment Period of approximately 14 weeks under the Contingent Design.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Subject voluntarily gives informed consent to participate in the study.
  2. Males and females aged 18 years or older at the time of informed consent.
  3. Females of childbearing potential must not be pregnant or lactating, and will either abstain from intercourse, or use two medically acceptable, highly-effective forms of contraception for the duration of study.
  4. Males with a partner of childbearing potential must agree to use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug.
  5. The subject has a clinical diagnosis of PH-COPD (WHO Group 3) using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria and post-bronchodilator spirometry.
  6. The subject has a resting peripheral capillary oxygen saturation (SpO2) ≥90%, with or without supplemental oxygen, not to exceed 10 L/min.
  7. The subject's baseline 6MWD must be at least 100 meters.
  8. Subjects are required to have a right heart catheterization (RHC) including a vasodilator test, with and without oxygen challenge, prior to randomization with the following documented parameters:
  9. Pulmonary vascular resistance (PVR) >4 Wood Units (WU) and
  10. A pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) of ≤15 mmHg
  11. A pulmonary arterial pressure mean (PAPm) of ≥30 mmHg
  12. Subjects on a chronic COPD medication therapy must be on a stable and optimized dose for ≥30 days prior to Screening Visit.
  13. Subjects on medications for conditions unrelated to COPD must be on a stable and optimized dose for ≥30 days prior to start of Screening Visit 1 and remain on stable doses throughout the Screening Period. Exceptions are anticoagulants and diuretics.
  14. In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing and likely to be cooperative with protocol requirements, including attending all study visits.

Exclusion Criteria

  1. The subject has a diagnosis of pulmonary arterial hypertension (PAH) or PH for reasons other than COPD.
  2. The subject has a confirmed diagnosis of WHO Group 3 PH, other than COPD.
  3. The subject has received any FDA approved therapy including: prostacyclin therapy, prostacyclin receptor agonist, endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor (PDE5-I), or soluble guanylate cyclase (sGC) within 60 days of Screening.
  4. The subject has previously been diagnosed with alpha-1 antitrypsin deficiency.
  5. The subject has shown intolerance to prostanoid therapy.
  6. The subject is unable to tolerate low dose (3 breaths, 18 mcg) study drug and/or unable to follow dosing regimen during the Screening Period.
  7. The subject has evidence of clinically significant left-sided heart disease. Note: Subjects with abnormal left ventricular function attributable entirely to impaired left ventricular filling due to the effects of right ventricular overload will not be excluded, but requires the Sponsor's approval.
  8. The subject is receiving > 10 L/min of oxygen supplementation by any mode of delivery at rest between the Screening Visit and Baseline Visit.
  9. Current use of any inhaled tobacco/marijuana products.
  10. Significant history of substance abuse within 6 months prior to start of Screening Visit.
  11. Exacerbation of COPD for active pulmonary or upper respiratory infection within 60 days prior to Screening Visit.
  12. Initiation of pulmonary rehabilitation within 12 weeks prior to the Screening Visit 1.
  13. The subject has an uncontrolled medical condition deemed by an Investigator to pose an undue risk to the subject.
  14. The subject has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale).
  15. The subject has a Body Mass Index ≥45 kg/m2 at Screening Visit 1.
  16. The subject has any musculoskeletal disorder or has any other condition that would limit ambulation.
  17. Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to Screening Visit 1.
  18. Any other clinically significant illness or abnormal laboratory value(s) that might adversely affect the interpretation of the study data.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Inhaled Treprostinil
Inhaled treprostinil delivered via an ultrasonic nebulizer with a target dosing regimen of 12 breaths (72 mcg) 4 times daily (QID)
  • Drug: Inhaled treprostinil solution
    Treprostinil inhalation solution
Placebo Comparator
Placebo
Placebo delivered via an ultrasonic nebulizer for QID administration
  • Drug: Placebo solution
    Placebo solution

Recruiting Locations

Banner University Medical Center
Phoenix, Arizona 85006
Contact:
Phillip Esther
602-521-3189
phillipesther@email.arizona.edu

More Details

NCT ID
NCT03496623
Status
Recruiting
Sponsor
United Therapeutics

Study Contact

Prakash Sista, Ph.D.
240-821-1661
304perfectstudy@lungbiotechnology.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.