Safety and Tolerability of Inhaled Treprostinil in Adult PH Due to COPD

A Prospective, Multicenter, Single-arm Study to Evaluate the Safety and Tolerability of Inhaled Treprostinil in Subjects With Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease

This is a multicenter, single-arm trial to evaluate the safety and efficacy of inhaled treprostinil in subjects with pre-capillary pulmonary hypertension (PH) associated with Chronic Obstructive Pulmonary Disease (COPD).

Study Overview

• Status: Withdrawn
• Conditions: Chronic Obstructive Pulmonary Disease; Pulmonary Hypertension
• Intervention / Treatment: Drug: Inhaled Treprostinil

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of WHO Group 3 PH associated with COPD

2. Subjects are required to have a right heart catheterization (RHC) within one year prior to the first dose of study drug with the following parameters:

   1. Pulmonary vascular resistance (PVR) ≥ 4 Wood Units (WU) and
   2. A left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedge pressure (PCWP) of ≤ 12 mmHg if PVR ≥ 4 WU to < 6.25 WU or ≤ 15 mmHg if PVR ≥ 6.25 WU and
   3. A mean pulmonary arterial pressure (mPAP) of ≥ 30 mmHg

3. Clinical Diagnosis of COPD will be made using accepted Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria, including Baseline spirometry with the following documented parameters:

   1. FEV1 < 65% predicted, and
   2. FEV1/ FVC < 70
4. Baseline 6MWD ≥ 100 meters

Exclusion criteria:

1. The subject has a diagnosis of pulmonary arterial hypertension (PAH) or PH for reasons other than COPD as outlined in inclusion criterion 3. This would include, but is not limited to, the concomitant presence of thromboembolic disease (acute or chronic), untreated or inadequately treated obstructive sleep apnea, connective tissue disease (including but not limited to systemic sclerosis/scleroderma, or systemic lupus erythematosus), sarcoidosis, interstitial lung disease,human immunodeficiency virus-1 infection, and other conditions under WHO Group 1, 2, 4, and 5 classifications.
2. The subject has received any Food and Drug Administration (FDA)-approved medication for the treatment of PAH (ie, prostacyclin, prostacyclin receptor agonist, endothelin receptor antagonist [ERA], phosphodiesterase type 5 inhibitor [PDE5-I],or soluble guanylate cyclase [sGC] stimulator) within 60 days of the first dose of study drug, except for acute vasoreactivity testing.

3. The subject has evidence of clinically significant left-sided heart disease as defined by the following criteria per the most recent assessment:

   1. Left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedge pressure (PCWP) >15 mmHg (or >12 mmHg if pulmonary vascular resistance [PVR] ≥4 to <6.25 WU)
   2. Left ventricular ejection fraction <40% as assessed by either angiography or echocardiography.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Inhaled Treprostinil; Active Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath.	Drug: Inhaled Treprostinil; Inhaled treprostinil (6 mcg/breath) administered four times daily; Other Names: Tyvaso

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events Among Participants through 48 Weeks	The incidence of adverse events among participants throughout the 48-week study will be measured by the number of participants analyzed and the percentage of those participants who experienced an adverse event.	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in 6-minute Walk Distance (6MWD) from Baseline to Week 48	Baseline and Week 48
Change in plasma concentration of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) from Baseline to Week 48	Baseline and Week 48
Change in Forced Expiratory Volume (FEV1) in One Second from Baseline to Week 48	Baseline and Week 48
Change in Forced Vital Capacity (FVC) from Baseline to Week 48	Baseline and Week 48
Change in Lung Diffusion Capacity (DLCO) from Baseline to Week 48	Baseline and Week 48
Change in right ventricular ejection fraction (RVEF) as assessed via cMRI from Baseline to Week 48	Baseline and Week 48

Collaborators and Investigators

• Sponsor: United Therapeutics

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2017
• Primary Completion (Anticipated): April 1, 2019
• Study Completion (Anticipated): April 1, 2019

Study Registration Dates

• First Submitted: December 22, 2016
• First Submitted That Met QC Criteria: January 5, 2017
• First Posted (Estimate): January 6, 2017

Study Record Updates

• Last Update Posted (Actual): April 11, 2017
• Last Update Submitted That Met QC Criteria: April 7, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: COPD; PH; Treprostinil; 6 Minute Walk Test
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Hypertension; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypertension, Pulmonary; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: RIN-PH-203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No