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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. Identifier: NCT03496623
Recruitment Status : Recruiting
First Posted : April 12, 2018
Last Update Posted : April 22, 2019
Information provided by (Responsible Party):
United Therapeutics

Tracking Information
First Submitted Date  ICMJE March 29, 2018
First Posted Date  ICMJE April 12, 2018
Last Update Posted Date April 22, 2019
Actual Study Start Date  ICMJE June 27, 2018
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03496623 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2018)
  • 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).
  • 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.
  • 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"
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Patients With PH Due to COPD
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Pulmonary Hypertension
  • Chronic Obstructive Pulmonary Disease
Intervention  ICMJE
  • Drug: Inhaled treprostinil solution
    Treprostinil inhalation solution
  • Drug: Placebo solution
    Placebo solution
Study Arms  ICMJE
  • Experimental: Inhaled Treprostinil
    Inhaled treprostinil delivered via an ultrasonic nebulizer with a target dosing regimen of 12 breaths (72 mcg) 4 times daily (QID)
    Intervention: Drug: Inhaled treprostinil solution
  • Placebo Comparator: Placebo
    Placebo delivered via an ultrasonic nebulizer for QID administration
    Intervention: Drug: Placebo solution
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 5, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

    1. Females of childbearing potential must not be pregnant or lactating, and will either abstain from intercourse, or use two medically acceptable, highly-effective forms of contraception for the duration of study.
    2. Males with a partner of childbearing potential must agree to use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug.
  3. The subject has a clinical diagnosis of PH-COPD (WHO Group 3) using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria and post-bronchodilator spirometry.
  4. The subject has a resting peripheral capillary oxygen saturation (SpO2) ≥90%, with or without supplemental oxygen, not to exceed 10 L/min.
  5. The subject's baseline 6MWD must be at least 100 meters.
  6. Subjects are required to have a right heart catheterization (RHC) including a vasodilator test, with and without oxygen challenge, prior to randomization with the following documented parameters:

    1. Pulmonary vascular resistance (PVR) >4 Wood Units (WU) and
    2. A pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) of ≤15 mmHg
    3. A pulmonary arterial pressure mean (PAPm) of ≥30 mmHg
  7. Subjects on a chronic COPD medication therapy must be on a stable and optimized dose for ≥30 days prior to Screening Visit.
  8. Subjects on medications for conditions unrelated to COPD must be on a stable and optimized dose for ≥30 days prior to start of Screening Visit 1 and remain on stable doses throughout the Screening Period. Exceptions are anticoagulants and diuretics.
  9. In the opinion of the Investigator, the subject is able to 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:

  1. The subject has a diagnosis of pulmonary arterial hypertension (PAH) or PH for reasons other than COPD.
  2. The subject has a confirmed diagnosis of WHO Group 3 PH, other than COPD.
  3. The subject has received any FDA approved therapy including: prostacyclin therapy, prostacyclin receptor agonist, endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor (PDE5-I), or soluble guanylate cyclase (sGC) within 60 days of Screening.
  4. The subject has previously been diagnosed with alpha-1 antitrypsin deficiency.
  5. The subject has shown intolerance to prostanoid therapy.
  6. The subject is unable to tolerate low dose (3 breaths, 18 mcg) study drug and/or unable to follow dosing regimen during the Screening Period.
  7. The subject has evidence of clinically significant left-sided heart disease. Note: Subjects with abnormal left ventricular function attributable entirely to impaired left ventricular filling due to the effects of right ventricular overload will not be excluded, but requires the Sponsor's approval.
  8. The subject is receiving > 10 L/min of oxygen supplementation by any mode of delivery at rest between the Screening Visit and Baseline Visit.
  9. Current use of any inhaled tobacco/marijuana products.
  10. Significant history of substance abuse within 6 months prior to start of Screening Visit.
  11. Exacerbation of COPD for active pulmonary or upper respiratory infection within 60 days prior to Screening Visit.
  12. Initiation of pulmonary rehabilitation within 12 weeks prior to the Screening Visit 1.
  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 ≥45 kg/m2 at Screening Visit 1.
  16. The subject has any musculoskeletal disorder or has any other condition that would limit ambulation.
  17. Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to Screening Visit 1.
  18. Any other clinically significant illness or abnormal laboratory value(s) that might adversely affect the interpretation of the study data.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Prakash Sista, Ph.D. 240-821-1661
Contact: Mary Lou Tomson, M.A. 240-821-1881
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03496623
Other Study ID Numbers  ICMJE RIN-PH-304
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party United Therapeutics
Study Sponsor  ICMJE United Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account United Therapeutics
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP