Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Patients With PH Due to COPD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03496623
Recruitment Status : Recruiting
First Posted : April 12, 2018
Last Update Posted : February 13, 2020
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Brief Summary:
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.

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 314 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : June 27, 2018
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Inhaled Treprostinil
Inhaled treprostinil delivered via an ultrasonic nebulizer with a target dosing regimen of 12 breaths (72 mcg) 4 times daily (QID)
Drug: Inhaled treprostinil solution
Treprostinil inhalation solution

Placebo Comparator: Placebo
Placebo delivered via an ultrasonic nebulizer for QID administration
Drug: Placebo solution
Placebo solution




Primary Outcome Measures :
  1. Change in 6-Minute Walk Distance (6MWD) from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    The intent of the 6-Minute Walk Test (6MWT) is a validated and reliable measure of exercise ability in patients with chronic respiratory diseases.


Secondary Outcome Measures :
  1. Change in Borg dyspnea score from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    The Borg dyspnea score is a 10 point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (no dyspnea at all) to 10 (very, very severe dyspnea).

  2. Change in quality of life (QOL) measured by St. George's Respiratory Questionnaire (SGRQ) from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    The SGRQ is a designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.

  3. Change in QOL measured by the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    The UCSD SOBQ is a self-administered rating of dyspnea associated with activities of daily living. The questionnaire uses a 6-point scale where 0 = "not at all" and 5 = "maximal or unable to do because of breathlessness"

  4. Change in plasma concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) levels from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants who meet the following criteria may be included in the study:

  1. Subject voluntarily gives informed consent to participate in the study.
  2. Males and females 18 years of age and above at the time of informed consent.

    1. 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, [<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. Subject must have a negative pregnancy test at the Screening Visit 1 (urine [prior to the first dose of study medication] and serum) and Baseline Visit (Study Week 1) (urine).
    2. 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.
  3. Diagnosis of PH-COPD (WHO Group 3).
  4. Clinical diagnosis of COPD will be made using the Global Initiative for Chronic

    Obstructive Lung Disease (GOLD) diagnostic criteria (GOLD Criteria 2019) and spirometry with the following documented parameters measured during Screening Visit 1 (prior to start of low-dose inhaled treprostinil):

    1. Forced expiratory volume in 1 second (FEV1) <80% predicted
    2. FEV1/Forced vital capacity (FVC) <70
  5. The subject has a resting saturation peripheral capillary oxygenation (SpO2) greater than or equal to 90%, with or without supplemental oxygen, but not to exceed 10 L/min oxygen supplementation by any mode of delivery at rest during Screening Visit 1.
  6. During Screening Visit 1 prior to start of low-dose inhaled treprostinil, a 6MWD greater than or equal to 100 meters.
  7. Have a right heart catheterization (RHC) performed during Screening Visit 1. (A previous RHC obtained 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:

    1. PVR greater than or equal to 4 Wood units
    2. A pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) of less than or equal to 15 mmHg
    3. A PAPm of greater than or equal to 30 mmHg
  8. Participants must be on a stable and optimized dose of chronic COPD medications for greater than or equal to 60 days prior to start of Screening Visit 1 and remain on the same dose throughout the Screening Period.
  9. Participants on medications for conditions unrelated to COPD must be on a stable and optimized dose for greater than or equal to 30 days prior to start of Screening Visit 1 and should remain on the same dose until the end of the study. Exceptions are anticoagulants and diuretics.
  10. In the opinion of the Investigator, the subject can communicate effectively with study personnel and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.

Exclusion Criteria:

The following will exclude participants from the study:

  1. The subject has a diagnosis of either pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) due to reasons other than COPD. This would include, but is 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.
  2. Based on chest CT imaging during Screening Visit 1, the subject has a confirmed diagnosis of WHO Group 3 PH, other than COPD, such as idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, diffuse parenchymal lung disease or interstitial lung disease. A previous chest CT scan performed within the 6 months prior to the start of Screening Visit 1 is also acceptable, and a repeat assessment is not required.

    A redacted CT scan report (from Screening Visit 1 or dated within prior 6 months) should be provided to the Medical Monitor with the Pre-Baseline Review Form to confirm eligibility.

  3. 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 start of Screening Visit 1, except if received for acute vasoreactivity testing.
  4. The subject has previously been diagnosed with alpha-1 antitrypsin deficiency.
  5. The subject has had any prior intolerance to prostanoid therapy.
  6. Inability to tolerate low-dose (3 breaths, 18 mcg) study drug and/or inability to follow dosing regimen during the Screening Period (pre-randomization).
  7. The subject 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. Note: Participants 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 Medical Monitor is needed.
  8. The subject is receiving >10 L/min of oxygen supplementation by any mode of delivery at rest.
  9. Currently using any inhaled tobacco products, electronic cigarettes, or inhaled substances, excluding prescribed respiratory therapies, unless approved by the Medical Monitor.
  10. Significant history of substance abuse within 6 months prior to start of Screening Visit 1.
  11. Any exacerbation of COPD (including hospitalization or outpatient therapy) or active pulmonary or upper respiratory infection 60 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. For the purpose of this protocol, treatment of sequalae of COPD are considered COPD exacerbation.
  12. 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 study Treatment Period.
  13. The subject has an uncontrolled medical condition deemed by an Investigator to pose an undue risk to the subject.
  14. The subject has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale).
  15. The subject has a Body Mass Index greater than or equal to 45 kg/m2 during Screening Visit 1.
  16. The subject has any musculoskeletal disorder (ie, arthritis of the lower limbs which limits ambulation, recent hip or knee joint replacement, artificial leg) or has any other condition that would likely be the primary limitation to ambulation.
  17. Use of any investigational drug/device or participation in any investigational study with therapeutic intent within 30 days prior to start of Screening Visit 1.
  18. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03496623


Contacts
Layout table for location contacts
Contact: Prakash Sista, Ph.D. 240-821-1661 304perfectstudy@lungbiotechnology.com
Contact: Mary Lou Tomson, M.A. 240-821-1881 304perfectstudy@lungbiotechnology.com

Locations
Show Show 51 study locations
Sponsors and Collaborators
United Therapeutics
Layout table for additonal information
Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT03496623    
Other Study ID Numbers: RIN-PH-304
First Posted: April 12, 2018    Key Record Dates
Last Update Posted: February 13, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by United Therapeutics:
Pulmonary Hypertension
COPD
Inhaled Treprostinil
6-Minute Walk Test
Tyvaso
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Hypertension, Pulmonary
Hypertension
Vascular Diseases
Cardiovascular Diseases
Respiratory Tract Diseases
Treprostinil
Pharmaceutical Solutions
Antihypertensive Agents