PERFECT OLE: Inhaled Treprostinil in Participants With Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (PH-COPD)

Sponsor

United Therapeutics (Industry)

Overall Status

Enrolling by invitation

CT.gov ID

NCT03794583

Collaborator

Lung Biotechnology PBC (Industry)

136

Enrollment

Locations

Arm

79.3

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open-label study will evaluate the safety of continued therapy with inhaled treprostinil in participants who have completed Study RIN-PH-304 (NCT03496623). This study hypothesizes that long-term safety findings will be similar to those observed in the randomized, placebo-controlled, double-blind, adaptive study 'A Phase 3, Randomized, Placebo-controlled, Double-blind, Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Patients with Pulmonary Hypertension due to Chronic Obstructive Pulmonary Disease (PH-COPD)(RIN-PH-304).

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Hypertension Chronic Obstructive Pulmonary Disease	Drug: Inhaled treprostinil solution	Phase 3

Detailed Description

This is a multi-center, open-label study for eligible participants who completed all scheduled study visits during the Treatment Period of Study RIN-PH-304.

Participants who provide informed consent for this open-label extension study on or prior to the final study visit of RIN-PH-304 may participate in the study, provided all other eligibility criteria are met. The RIN-PH-304 final study visit and the RIN-PH-305 Enrollment Visit will occur on the same day.

All participants will reinitiate inhaled treprostinil at 3 breathes (18 micrograms [mcg]) 4 times daily (QID) during waking hours. Study drug doses should be maximized to tolerability throughout the study, and dose titrations should occur as rapidly as possible (as directed by the Investigator) with a target dosing regimen of 15 breaths QID or the maximum tolerated dose.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

136 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This trial is not blinded. All participants will begin titration of study drug once all entry criteria have been met.This trial is not blinded. All participants will begin titration of study drug once all entry criteria have been met.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label Extension Study of Inhaled Treprostinil in Patients With Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (PH-COPD)

Actual Study Start Date :

Dec 21, 2018

Anticipated Primary Completion Date :

Jul 31, 2025

Anticipated Study Completion Date :

Jul 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Inhaled Treprostinil Solution Inhaled treprostinil solution (0.6 milligrams per milliliter [mg/mL], 6 mcg/breath) QID during waking hours.	Drug: Inhaled treprostinil solution Inhaled treprostinil solution per dose and schedule specified in the arm

Arm

Intervention/Treatment

Experimental: Inhaled Treprostinil Solution

Inhaled treprostinil solution (0.6 milligrams per milliliter [mg/mL], 6 mcg/breath) QID during waking hours.

Drug: Inhaled treprostinil solution

Inhaled treprostinil solution per dose and schedule specified in the arm

Outcome Measures

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From enrollment to end of study, estimated up to 2 years.]

Secondary Outcome Measures

6 Minute Walk Distance (6MWD) [Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.]
Participants will be instructed to walk down a corridor at a comfortable speed as far as they can manage for six minutes. Distance <500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance >800 meters (with no rests) suggests mild or no limitation.
Borg Dyspnea Score [Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.]
The modified 0-10 category-ratio Borg scale is one in which the participants rate the maximum level of dyspnea they experienced during the Six Minute Walk Test (6MWT). Scores range from 0 (for the best condition) and 10 (for the worst condition).
N-terminal Pro-brain Natriuretic Peptide (NT-pro-BNP) [Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.]
The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function.
Saturation Peripheral Capillary Oxygenation (SpO2) [Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.]
SpO2 will be assessed via pulse oximetry.
Heart Rate [Assessed at enrollment, Week 6, and then every 12 weeks through study completion, estimated up to 2 years.]
Heart rate will be assessed via pulse oximetry
Change in Baseline in Patient Global Assessment (PGA) [Week 6, Year 1 or Discontinuation Visit (whichever occurs first)]
The PGA is used to rate participant fatigue and shortness of breath. Participants will use the Sponsor-provided smart device for at-home capture of PGA data.
Change from Baseline in Actigraphy [Baseline, Week 6, Year 1 or Discontinuation Visit (whichever occurs first)]
Daily physical activity, including overall, non-sedentary, and moderate to vigorous physical activity will be measured via a wrist-worn medical grade physical activity monitor (actigraph).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant voluntarily gives informed consent to participate in the study.
Participant completed Study RIN-PH-304.
Women of childbearing potential (defined as less than 1 year post-menopausal 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 low failure rate, [less than 1% per year], such as approved hormonal contraceptives, barrier methods [such as 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.
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.

Exclusion Criteria:

The participant is pregnant or lactating.
The participant was prematurely discontinued from Study RIN-PH-304.
The participant is intolerant to inhaled prostanoid therapy.
The participant is unwilling or unable to use Sponsor-provided devices (actigraph, spirometer, or smart device).
The participant is scheduled to receive another investigational drug, device, or therapy during the course of this study.
Any other clinically significant illness or abnormal laboratory value(s) that, in the opinion of the Investigator, might adversely affect the interpretation of the study data.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of California Davis Medical Center	Sacramento	California	United States	95817
3	St. Francis Sleep Allergy & Lung Institute	Clearwater	Florida	United States	33765
4	St. Vincent's Lung, Sleep, and Criticial Care Specialists	Jacksonville	Florida	United States	32204
5	Pulmonary & Critical Care of Atlanta	Atlanta	Georgia	United States	30342
6	Georgia Clinical Research	Austell	Georgia	United States	30106
7	University of Illinois Medical Center	Chicago	Illinois	United States	60612
8	St. Vincent Medical Group, Inc.	Indianapolis	Indiana	United States	46260
9	Kentuckiana Pulmonary Associates	Louisville	Kentucky	United States	40202
10	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
11	Spectrum Health	Grand Rapids	Michigan	United States	49546
12	Albany Medical Center	Albany	New York	United States	12208
13	Mount Sinai Medical Center	New York	New York	United States	10029
14	University of Rochester Medical Center	Rochester	New York	United States	14623
15	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
16	The Carl and Edyth Lindner Research Center at The Christ Hospital	Cincinnati	Ohio	United States	45219
17	Cleveland Clinic	Cleveland	Ohio	United States	44195
18	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
19	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
20	Medical University of South Carolina	Charleston	South Carolina	United States	29425
21	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
22	Pulmonary Associates of Richmond, Inc.	Richmond	Virginia	United States	23230
23	Carilion Clinic	Roanoke	Virginia	United States	24014
24	University of Wisconsin School of Medicine and Public Health	Madison	Wisconsin	United States	53792
25	Lady Davis Carmel Medical Centre	Haifa		Israel	34362
26	Hadassah-Hebrew University Hospital	Jerusalem		Israel	9112001
27	Rabin Medical Center	Petah Tiva		Israel	49100