Patient Global Impression Questions for Activity-Induced Symptoms in Participants With PAH

NCT03888365 | Completed Results

• 1 other identifier: RIN-PRN-201
• Study Type: observational
• Target: 43
• Locations: 1 country
• Sites: 10

Brief Summary

This is an observational, multicenter, single-day, Phase 2 study. This study will include a 14-day Screening Period and Study Day 1 clinic visit. Participants will be required to perform an activity to induce symptoms of PAH, and participants' severity of self-reported symptoms of PAH will be measured from pre-activity, immediately after the activity, and through the 30-minute recovery. Participants will be asked about their PAH symptoms using 3 PGI-S questions that address their overall PAH symptoms, shortness of breath, and physical fatigue.

Conditions

Pulmonary Arterial Hypertension

Keywords

Hypertension; Treprostinil; Pulmonary Hypertension; Lung Diseases

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Patient Global Impression of Severity (PGI-S) Score in Cohort A Participants at Approximately 30 Minutes of Previous Dose of Inhaled Treprostinil (the Expected Peak Level) on Day 1

  A global index that consists of 3 questions to which participants will rate the severity of 1) their PAH symptoms, 2) shortness of breath (SOB), and 3) fatigue. The minimum and maximum range of scores for each of the 3 individual questions was 1-5, with severity scale choices of 1=Not present, 2=Mild, 3=Moderate, 4=Severe, and 5=Very Severe. A higher score indicated worse outcome. The Baseline is defined as the average respective severity rating measured at 15 minutes and 0 minute prior to the ISWT. In the case of a single, missing severity rating measured pre-ISWT, the other non-missing single severity rating would be used as baseline value. Only participants with both a measurement at baseline and at the given post-baseline visit are summarized. Change from Baseline = Post-Baseline value - Baseline value. Peak levels are the highest concentrations of a drug in plasma.

  Baseline, Approximately 30 m of previous dose of inhaled treprostinil (the expected peak level) on Day 1

• Change From Baseline in PGI-S Score in Cohort A Participants at Approximately 3-4 Hours of Previous Dose of Inhaled Treprostinil (the Expected Trough Level) on Day 1

  A global index that consists of 3 questions to which participants will rate the severity of 1) their PAH symptoms, 2) SOB, and 3) fatigue. The minimum and maximum range of scores for each of the 3 individual questions was 1-5, with severity scale choices of 1=Not present, 2=Mild, 3=Moderate, 4=Severe, and 5=Very Severe. A higher score indicated worse outcome. The Baseline is defined as the average respective severity rating measured at 15 minutes and 0 minute prior to the ISWT. In the case of a single, missing severity rating measured pre-ISWT, the other non-missing single severity rating would be used as baseline value. Only participants with both a measurement at baseline and at the given post-baseline visit are summarized. Change from Baseline = Post-Baseline value - Baseline value. Trough levels are the lowest concentrations of a drug in plasma.

  Baseline, Approximately 3-4 h of previous dose of inhaled treprostinil (the expected trough level) on Day 1

• Change From Baseline in PGI-S Score in Cohort B Participants at Approximately 4 Hours After Morning Dose of Non-Treprostinil PAH Medication (Period 1) on Day 1

  A global index that consists of 3 questions to which participants will rate the severity of 1) their PAH symptoms, 2) SOB, and 3) fatigue. The minimum and maximum range of scores for each of the 3 individual questions was 1-5, with severity scale choices of 1=Not present, 2=Mild, 3=Moderate, 4=Severe, and 5=Very Severe. A higher score indicated worse outcome. The Baseline is defined as the average respective severity rating measured at 15 minutes and 0 minute prior to the ISWT. In the case of a single, missing severity rating measured pre-ISWT, the other non-missing single severity rating would be used as baseline value. Only participants with both a measurement at baseline and at the given post-baseline visit are summarized. Change from Baseline = Post-Baseline value - Baseline value.

  Baseline, Approximately 4 h after morning dose of non-treprostinil PAH medication (Period 1) on Day 1

• Change From Baseline in PGI-S Scores in Cohort B Participants With an ISWT at Least 1 h Following Completion of Previous ISWT (Period 2) on Day 1

  A global index that consists of 3 questions to which participants will rate the severity of 1) their PAH symptoms, 2) SOB, and 3) fatigue. The minimum and maximum range of scores for each of the 3 individual questions was 1-5, with severity scale choices of 1=Not present, 2=Mild, 3=Moderate, 4=Severe, and 5=Very Severe. A higher score indicated worse outcome. The Baseline is defined as the average respective severity rating measured at 15 minutes and 0 minute prior to the ISWT. In the case of a single, missing severity rating measured pre-ISWT, the other non-missing single severity rating would be used as baseline value. Only participants with both a measurement at baseline and at the given post-baseline visit are summarized. Change from Baseline = Post-Baseline value - Baseline value.

  Baseline, At least 1 h following completion of previous ISWT (Period 2) on Day 1

Secondary Outcomes (1)

• Change From Baseline in Modified Borg Dyspnea Scores at Day 1

  Baseline, ~30 m of previous dose of inhaled treprostinil, ~3-4 h of previous dose of inhaled treprostinil, ~4 h after morning dose of non-treprostinil PAH medication, and ≥1 h following completion of previous ISWT on Day 1

Other Outcomes (2)

• Change From Baseline in Pulse Oximetry at Day 1

  Baseline, ~30 m of previous dose of inhaled treprostinil, ~3-4 h of previous dose of inhaled treprostinil, ~4 h after morning dose of non-treprostinil PAH medication, and ≥1 h following completion of previous ISWT on Day 1

• Change From Baseline in Heart Rate at Day 1

  Baseline, ~30 m of previous dose of inhaled treprostinil, ~3-4 h of previous dose of inhaled treprostinil, ~4 h after morning dose of non-treprostinil PAH medication, and ≥1 h following completion of previous ISWT on Day 1

Study Arms (2)

Cohort A: Treprostinil

Participants who are currently prescribed and using inhaled treprostinil for the treatment of PAH.

Drug: Treprostinil

Cohort B: Non-Treprostinil PAH Medications

Participants who are taking other PAH medications (instead of inhaled treprostinil).

Drug: Non-Treprostinil PAH Medications

Interventions

Treprostinil DRUG

Treprostinil treatment will be at the discretion of the participant's physician, and determined on an individual basis.

Cohort A: Treprostinil

Non-Treprostinil PAH Medications DRUG

Non-treprostinil treatment will be at the discretion of the participant's physician, and determined on an individual basis.

Cohort B: Non-Treprostinil PAH Medications

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Males and females aged 18 years and above with a diagnosis of PAH that is either idiopathic or familial PAH (World Health Organization \[WHO\] Group 1), collagen vascular disease associated PAH, PAH associated with human immunodeficiency virus (HIV) infection, PAH induced by anorexigens/toxins, or PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥1 years).

You may qualify if:

• Participant voluntarily gives informed consent to participate in the study.
• Males and females aged 18 years and above at the time of informed consent.
• Established primary diagnosis of PAH that is either idiopathic or familial PAH (WHO Group 1), collagen vascular disease associated PAH, PAH associated with HIV infection, PAH induced by anorexigens/toxins, or PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥1 years).
• Participant is deemed WHO Functional Class 1, 2, or 3.
• Participant has shortness of breath upon exertion (exhibits a ≥1-point change in Borg dyspnea score) as assessed by the ISWT and a minimum completion of 3 shuttles (30 meters) of the ISWT. Participant may have other symptoms as well.
• Participant is on stable dose of all FDA-approved PAH treatments (exceptions are anticoagulants and diuretics) for at least 60 days prior to Screening.
• In the opinion of the Investigator, the participant can communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements.

You may not qualify if:

• The participant is known to be pregnant or nursing.
• The participant has 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.
• The participant has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale).
• The participant has any ambulatory or orthopedic limitations that would interfere with the ability to perform the activity.
• The participant has been hospitalized within 30 days of Screening.
• Current use of prostacyclin analogs/agonists, except inhaled treprostinil, for the treatment of PAH.
• Use of any other investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days of Screening (concurrent participation in registry studies is allowed).
• Any other clinically significant illness that, in the opinion of the Investigator, might put the participant at risk of harm during the study or might adversely affect the interpretation of the study data.

Sponsors & Collaborators

• United Therapeutics: lead
• Lung Biotechnology PBC: collaborator

Study Sites (10)

The University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

Santa Barbara Pulmonary Associates

Santa Barbara, California, 93105, United States

Location

St. Francis Sleep, Allergy & Lung Institute

Clearwater, Florida, 33765, United States

Location

Pulmonary & Critical Care of Atlanta

Atlanta, Georgia, 30342, United States

Location

Kentuckiana Pulmonary Associates

Louisville, Kentucky, 40202, United States

Location

Pulmonary Health Physicians, PC

Fayetteville, New York, 13066, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27517, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension; Hypertension, Pulmonary; Lung Diseases

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Lung Biotechnology PBC Study Director
• Organization: Lung Biotechnology PBC

info@lungbiotechnology.com

301-608-9292

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: March 25, 2019
• Study Start: April 1, 2019
• Primary Completion: September 19, 2019
• Study Completion: September 19, 2019
• Last Updated: March 16, 2021
• Results First Posted: March 16, 2021

Record last verified: 2021-02

Locations

US (10)