A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Patients With PH Due to COPD
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.
- Pulmonary Hypertension
- Chronic Obstructive Pulmonary Disease
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Subject voluntarily gives informed consent to participate in the study.
- Males and females aged 18 years or older at the time of informed consent.
- 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.
- 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.
- 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.
- The subject has a resting peripheral capillary oxygen saturation (SpO2) ≥90%, with or without supplemental oxygen, not to exceed 10 L/min.
- The subject's baseline 6MWD must be at least 100 meters.
- 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:
- Pulmonary vascular resistance (PVR) >4 Wood Units (WU) and
- A pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) of ≤15 mmHg
- A pulmonary arterial pressure mean (PAPm) of ≥30 mmHg
- Subjects on a chronic COPD medication therapy must be on a stable and optimized dose for ≥30 days prior to Screening Visit.
- 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.
- 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.
- The subject has a diagnosis of pulmonary arterial hypertension (PAH) or PH for reasons other than COPD.
- The subject has a confirmed diagnosis of WHO Group 3 PH, other than COPD.
- 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.
- The subject has previously been diagnosed with alpha-1 antitrypsin deficiency.
- The subject has shown intolerance to prostanoid therapy.
- 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.
- 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.
- The subject is receiving > 10 L/min of oxygen supplementation by any mode of delivery at rest between the Screening Visit and Baseline Visit.
- Current use of any inhaled tobacco/marijuana products.
- Significant history of substance abuse within 6 months prior to start of Screening Visit.
- Exacerbation of COPD for active pulmonary or upper respiratory infection within 60 days prior to Screening Visit.
- Initiation of pulmonary rehabilitation within 12 weeks prior to the Screening Visit 1.
- The subject has an uncontrolled medical condition deemed by an Investigator to pose an undue risk to the subject.
- The subject has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale).
- The subject has a Body Mass Index ≥45 kg/m2 at Screening Visit 1.
- The subject has any musculoskeletal disorder or has any other condition that would limit ambulation.
- Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to Screening Visit 1.
- Any other clinically significant illness or abnormal laboratory value(s) that might adversely affect the interpretation of the study data.
- Phase 3
- Study Type
- Intervention Model
- Crossover Assignment
- Primary Purpose
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
|Inhaled treprostinil delivered via an ultrasonic nebulizer with a target dosing regimen of 12 breaths (72 mcg) 4 times daily (QID)||
|Placebo delivered via an ultrasonic nebulizer for QID administration||
- NCT ID
- United Therapeutics
Study ContactPrakash Sista, Ph.D.