Inclusion Criteria:

• Subject voluntarily gives informed consent to participate in the study.
• Males and females 18 years of age and above at the time of informed consent:
  • Females of childbearing potential (defined as less than 1 year postmenopausal and not surgically sterile) must agree to practice abstinence or use 2 highly effective methods of contraception (defined as a method of birth control that results in a less than 1% per year failure rate, such as approved hormonal contraceptives, barrier methods [condom or diaphragm] used with a spermicide, or an intrauterine device) for the duration of study treatment and for 48 hours after discontinuing study drug. Subjects must have negative pregnancy tests at Screening Visit 1 (urine [prior to the first dose of study drug] and serum) and the Baseline Visit (urine [Study Week 1]);
  • Males with a partner of childbearing potential must agree to use a barrier method (condom) with a spermicide for the duration of treatment and for at least 48 hours after discontinuing study drug.
• Diagnosis of PH-COPD (WHO Group 3).
• Clinical diagnosis of COPD per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria (2020) and documented spirometry parameters measured during Screening Visit 1 (prior to start of low dose inhaled treprostinil), as follows:
  • Forced expiratory volume in 1 second (FEV1) < 80% predicted;
  • FEV1/Forced vital capacity (FVC) < 70.
• Resting saturation peripheral capillary oxygenation (SpO2) ≥ 90% during Screening Visit 1, with or without supplemental oxygen, and supplemental oxygen cannot exceed 10 L/min by any mode of delivery.
• A 6MWD ≥ 100 meters during Screening Visit 1 (prior to start of low dose inhaled treprostinil).
• Willing to undergo right heart catheterization (RHC) during Screening Visit 1. A RHC performed within 12 months prior to the start of Screening Visit 1 is acceptable for determining eligibility, even if done without oxygen or vasodilator challenge, and a repeat RHC is not required. The following parameters must be documented for eligibility:
  • Pulmonary vascular resistance (PVR) ≥ 4 Wood units;
  • Pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) of < 15 mmHg;
  • Pulmonary artery pressure mean (PAPm) of ≥ 30 mmHg.
  • Must be on a stable and optimized dose of chronic COPD medications for ≥ 30 days prior to the start of Screening Visit 1 and remain on the same dose throughout the Screening Period.
  • Can communicate effectively with study personnel and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits, in the opinion of the Investigator.

Exclusion Critieria:

• A diagnosis of either pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) due to reasons other than COPD, including, but not limited to, chronic thromboembolic PH or acute/recent deep vein thrombosis or pulmonary embolism, untreated or inadequately treated obstructive sleep apnea, connective tissue disease (including, but not limited to, systemic sclerosis/scleroderma or systemic lupus erythematosus), sarcoidosis, human immunodeficiency virus-1 infection, and other conditions under WHO Group 1, 2, 4, and 5 classifications.
• A confirmed diagnosis of idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, diffuse parenchymal lung disease, or interstitial lung disease, based on chest CT imaging during Screening Visit 1. A chest CT performed within 6 months prior to the start of Screening Visit 1 is acceptable for determining eligibility and a repeat assessment is not required. A redacted CT scan report (from Screening Visit 1 or dated within 6 months prior) should be provided to the Sponsor’s Medical Monitor with the Pre-Baseline Review Form to confirm eligibility.
• Received any Food and Drug Administration (FDA)-approved medication for the treatment of PAH (i.e., prostacyclin, prostacyclin receptor agonist, endothelin receptor antagonist [ERA], phosphodiesterase type 5 inhibitor [PDE5-I], or soluble guanylate cyclase [sGC] stimulator) at Screening Visit 1 and thereafter, except if received for acute vasoreactivity testing.
• Previous diagnosis of homozygous alpha-1 antitrypsin deficiency.
• Any prior intolerance to inhaled prostanoid therapy.
• Inability to tolerate low dose inhaled treprostinil and/or follow dosing regimen during the Screening Period (pre-randomization).
• Unwilling or unable to use Sponsor-provided devices (actigraph, spirometer, or smart device).
• Evidence of clinically significant left-sided heart disease (including, but not limited to, left ventricular ejection fraction < 40%, left ventricular hypertrophy) or clinically significant cardiologic conditions, such as congestive heart failure, coronary artery disease, or valvular heart disease.
  • NOTE: Subjects with abnormal left ventricular function attributable to the effects of right ventricular overload will not be excluded, but a discussion with and approval by the Sponsor’s Medical Monitor is required.
• Any exacerbation of COPD (including hospitalization or outpatient therapy) or active pulmonary or upper respiratory infection from 30 days prior to start of Screening Visit 1 through the Baseline Visit. This is defined as worsening of respiratory symptoms that required treatment with corticosteroids and/or antibiotics.
• Initiation of pulmonary rehabilitation within 12 weeks prior to start of Screening Visit 1 or, in the opinion of the Investigator, pulmonary rehabilitation is likely to be needed during the Treatment Period.
• Any form of congenital heart disease (repaired or unrepaired) other than a patent foramen ovale.
• Any musculoskeletal disorder (i.e., severe arthritis of the lower limbs which limits ambulation, recent hip or knee joint replacement, artificial leg) or any other condition that would likely be the primary limitation to ambulation.
• Use of any other investigational drug or device within 30 days prior to the start of Screening Visit 1.
• Any other clinically significant illness or abnormal laboratory value(s) measured during the Screening Period that, in the opinion of the Investigator, might adversely affect the interpretation of the study data or safety of the subject.